The holidays arrive with snow, slush and in-laws, so you decide to head somewhere warm. You tell your agentic AI assistant everything you want from your Caribbean vacation: activity choices, restaurant types to consider, the lodging and flight options you want. It searches and then, just like that, books everything without you ever having to click Buy.Midwinter heaven for you. Hell for your payment company's fraud detection team—which now must determine if these purchases were actually authorized or fraud perpetrated by some nefarious, margarita-thirsty identity thief."Historically, and currently for most commerce, the signal of intent for a consumer is tapping their card, clicking Buy on a website—[but] with agentic commerce, there is a delegation of authority," says Craig Vosburg, chief services officer and vice chairman of Mastercard. The company, he says, is positioning itself as "the operating system of economies,” through a cluster of new financial creations, which include: establishing a new stablecoin to instantly enable international transactions between different regions and currencies; creating "insight tokens" where you authorize an AI agent or a merchant to learn about your habits and preferences; and building B2B agentic payments for machines, with huge volumes of continuous business transactions.These are just some of the major advances driving Mastercard to No. 10 on Forbes' brand-new list: America's Most Innovative Large Companies.ForbesThe very notion of “Innovative” is, of course, inherently subjective. But with this new list, Forbes relies solely on hard data that capture dozens of different indicators of sector-leading innovation no matter their industry or age.The ranking is driven by Forbes’ new Innovation Index™, which measures innovation based on volume of patents and intellectual property, research focus, investor confidence, return on equity, media and social media sentiment, and evaluation of company news and statements by synthetic audiences (more on that later). The Index analyzes every company in the Standard & Poor’s 500 list, with the top 100 making the Forbes list More on the methodology can be found here. Led by pharma giant Eli Lilly (No. 1) and tech titan Apple (No. 2), the top 10 includes sectors as diverse as manufacturing (Boeing, No. 8) and financial services (Mastercard). But whether it's through R&D investments, market and consumer confidence, and/or the creation of new IP, they all outpace their peers in driving America's business engines forward.Lilly tops the list in part because of the spread and speed of its new-drug production. That new GLP-1 antagonist weight-loss pill, the first on the market, that one you’re constantly seeing ads for? That’s Lilly. (The company also produces popular GLP-1 inhibitor injections Mounjaro and Zepbound.) Other advances include promising treatments for early Alzheimer’s, breast cancer and migraines.The company’s next weight-loss drug, Retatrutide, targets three different receptors at once (GIP, GLP-1 and glucagon), and in phase 3 human trials saw an average body-weight loss of 28%, the kind of numbers to this point mostly seen by surgery. No wonder investors are bullish on the company, boosting its stock price by 79% in the past year and fueling its $1.17 trillion market cap.Daniel Skovronsky, Lilly's chief scientific and product officer and president of Lilly Research Laboratories, said the company has focused on hard-to-treat diseases, on speeding up drug studies and on creating broader access to its medicines worldwide. “Innovation isn't just a slogan,” he says. “Our daily work is turning science into medicines.”At Amazon (No. 6), company officials credit innovation for the firm’s dominance in retail and data services. Tye Brady, chief technologist for Amazon Robotics, gives the example of the company’s artificially intelligent Proteus robots, which launched in June and are now used in about 25 of the company’s 300 robotics-assisted facilities.Amazon’s challenge was to automate getting loaded-up racks of packages, called Go Carts, from sorting chutes to the proper docks for the proper trucks at the proper times—all while independently (and safely) navigating around humans working the docks. Amazon builds more mobile robots than any other company, Brady says, to address issues just like these. Proteus, which looks a little like a Roomba on steroids, uses a fleet of sensors hooked up to an onboard AI-powered computer brain.“Think of a cocktail party,” Brady says. “Everyone’s sitting there chit-chatting, and it’s hard to navigate your way around the room. People are really good at [thinking], ‘Hey, I got to get to the far end of the room because there’s a delicious cocktail in the far corner.’ Imagine being a robot trying to do that.”In the case of Proteus, the robot swiftly smacked into a problem, but it wasn’t technical: Curious human warehouse workers would gather around during testing to examine the friendly-looking little AI robots shouldering their 900-pound cages full of packages and would unwittingly prevent them from their appointed rounds. Amazon had given the robots lights to show workers where they wanted to go, and eyes to be more welcoming. After the tests, they made a few tweaks.“Now it’ll look up at you to say, ‘We’re waiting here.’ And if it gets really impatient, it may make R2D2-like sounds, a chirp chirp chirp chirp—‘Excuse me, trying to get my job done here,’” Brady says. Fortunately, people soon got used to seeing lots of Proteus robots moving around at once in the factories where it now serves. “Now it’s kind of blending into the woodwork.”An Amazon employee in Mt. Juliet, Tenn., works alongside the artifically intelligent Proteus robot, the all-but-smiling critter delivering packages to his right.Amazon RoboticsNo major feature on innovative companies would be complete without a little innovation of our own: For the first time, Forbes turned to an AI-based data source as one input into a list. The Forbes Most Innovative Large Companies list measures how synthetically-created audiences of investors, analysts, journalists and customers, based on real people and built using their previous writing in a variety of situations, responded to thousands of real company announcements—such as Amazon’s Proteus press release—as well as social and blog posts, leadership statements and earnings calls from the past few years.This data was provided by Kumkuat AI, a synthetic audience company founded this year that performs this analysis with archetypes for each industry. The results included some surprises, says Shann Biglione, Kumkuat’s co-founder. Take Boeing, which despite recent high-profile safety issues scored highly in how synthetic audiences reacted to its innovations."There's a very strong narrative score on how the company talks about its innovation, the commitment there is behind it, how the CEO [Kelly Ortberg] gets behind it," Biglione says. "Boeing is an interesting company that has a chance of turnaround over the next few years, if its innovation delivers."Boeing also scored well on analysis from Forbes data partner IPQwery, an intellectual property data firm that tracks companies’ patents and trademark activity. Frédérik Lacharité, IPQwery’s president and chief technology officer, says he is impressed by Boeing’s breadth of patents."They touch a lot of points, from engineering to systems to management to software," he says. "These are all offshoots that come from their technology."Biglione says he was surprised to see some firms that fly under the mainstream-media radar perform extraordinarily well in audience reaction, such as Lumentum, a communications tech company that ranks No. 76 on the Forbes list. Synthetic audiences reacted strongly to Lumentum’s laser-based tech that is used for things like facial recognition on iPhones.Even better-known names on the list, like Mastercard, intrigued our experts with the breadth of their innovative activity. "I'm surprised that they have that many patents, for a financial company, because I would expect them to have more trademarks than patents," Lacherité says, listing the variety of patents Mastercard registered recently. "Tokenization. Transactions. Preventing network security threats. Payment cards. Microchips. Biometrics …""Innovation is not a birthright," Mastercard’s Vosburg says. "It's something we work hard to cultivate. We need to fully embrace the challenge and the opportunity innovation presents."More From ForbesForbesJosh Kushner’s Fortune Tripled This Year Thanks To Stakes In OpenAI, SpaceX And MoreBy Giacomo TogniniForbesTikTok Profits Off Drug Dealer Ads For Cocaine, Opioids And XanaxBy Iain MartinForbesInside PayPal Mafia Billionaire Max Levchin’s Slow-And-Steady Path To Fintech ProfitabilityBy Jeff KauflinForbesPurely Elizabeth Founder Sells To Ferrero For $850 Million: “Feel The Fear And Do It Anyway”By Chloe Sorvino