Recent studies suggest that all prosthetic valves are at least mildly stenotic and may cause relatively high pressure gradients despite normal prosthesis function; such gradients could be due to a mismatch between prosthesis effective orifice area and patient's body size. In order to address this problem more directly, we derived, using a physiologic pulse duplicator system, the theoretical relations between transprosthetic pressure gradients and prosthesis effective orifice areas indexed for body surface area, assuming a normal resting cardiac index of 3.0 l/min m-2 and 10-50% increases in stroke volume such as may occur during maximal upright exercise. These exponential relations show that a small decrease in indexed effective orifice area produces a large increase in pressure gradient, and that the indexed effective orifice area should ideally be not less than 0.9-1.0 cm2/m2 for aortic prostheses and 1.3-1.5 cm2/m2 for mitral prostheses in order to minimize postoperative gradients. Thus, high postoperative gradients do not necessarily indicate intrinsic prosthesis dysfunction but may also be due to patient prosthesis mismatch. Intrinsic prosthetic performance is best assessed by comparing in vivo calculated effective orifice areas to in vitro measurements for same type and size of prosthesis. Patient prosthesis mismatch can be avoided by calculating before operation the projected indexed effective orifice area of the prosthesis being implanted.