Optimal valve orientation for Medtronic Hall (MH) and St. Jude Medical (SJM) mechanical aortic valve substitutes has been defined in animal experiments. This study evaluates hemodynamic performance of these two valves when implanted in their optimal orientation in humans. In a randomized prospective study, MH and SJM valves (size >23 mm) were implanted in 24 patients. Downstream turbulence and pressure gradients were measured intraoperatively and at six months postoperatively; pressure gradients and left ventricular mass regression were investigated. Intraoperative turbulence and pressure gradients were significantly lower for the MH valve. At follow up, pressure gradients again showed lower values for the MH, and this led to acceleration of left ventricular mass regression. In conclusion, these results indicate that the tilting disc valve shows superior hemodynamic performance to the bileaflet valve when both valves are implanted in their optimal orientation.