When aortic valve replacement is needed, a biological valve is usually implanted in patients older than age 60 to 65 years. A large valvular opening area is important to avoid prosthesis–patient mismatch and facilitate reverse left ventricular remodeling. The Trifecta biological valve (St Jude Medical, St Paul, Minn) is, because of its design, believed to reduce transvalvular gradient compared with other biological valves, especially in smaller annuli. Several retrospective studies have compared transvalvular gradients of implanted valves prostheses using the respective manufacturers given size and not the actual annulus size measured by a metric sizer. This makes comparison of the hemodynamic properties of different valve brands and sizes difficult. We therefore performed a prospective randomized study, using the same metric sizer to measure annulus size, and compared hemodynamic profiles of the Trifecta to our standard Mosaic Ultra biological valve (Medtronic, Minneapolis, Minn). Ninety elective patients with small to medium annulus diameter undergoing aortic valve replacement were randomized to either Trifecta or Mosaic Ultra. After native valve removal and decalcification, a Hegar-sizer was used to measure true annulus size. Then the largest possible valve of either brand was implanted according to the randomization protocol. Echocardiography was performed 6 months postoperatively. Baseline parameters of the 2 cohorts were comparable. There were lower transvalvular gradients in the Trifecta compared with the Mosaic Ultra group for the given annulus sizes. Severe prosthesis–patient mismatch was present in 28% of patients in the Mosaic group and 3% of patients in the Trifecta group. Trifecta showed lower transvalvular gradients and less severe prosthesis–patient mismatch compared with Mosaic Ultra for the given annulus sizes. ClinicalTrials.gov Protocol ID: 2011/2596/REK.