An anatomically approximate prosthetic heart valve includes dissimilar flexible leaflets, dissimilar commissures and/or a non-circular flow orifice. The heart valve may be implanted in the mitral position and have one larger leaflet oriented along the anterior aspect so as to mimic the natural anterior leaflet. Two other smaller leaflets extend around the posterior aspect of the valve. A basic structure providing peripheral support for the leaflets includes two taller commissures on both sides of the larger leaflet, with a third, smaller commissure between the other two leaflets. The larger leaflet may be thicker and/or stronger than the other two leaflets. The base structure defines a flow orifice intended to simulate the shape of the mitral annulus during the systolic phase.