Yes, you can use an American Express (Amex) card to rent a vehicle at Enterprise Rent-A-Car in 2026. Enterprise is one of the world's largest rental agencies and accepts all major credit cards, including Visa, Mastercard, and Discover, alongside Amex. Using an Amex card can be particularly beneficial for travelers because many American Express cards (such as the Gold or Platinum) provide Secondary Car Rental Loss and Damage Insurance as a standard benefit. Some higher-end Amex cards even allow you to enroll in a "Premium Car Rental Protection" program for a small flat fee per rental, which acts as primary insurance. However, when you pick up the car, Enterprise will place a "hold" (security deposit) on your Amex card, which typically covers the estimated cost of the rental plus a set amount (often $200-$500). This hold will be released once the car is returned in good condition. Always ensure the name on the Amex card matches the name on your driver's license to avoid any issues at the rental counter.