Background: Mechanical stress is one of the contributing factors for bioprosthetic calcification. A HeartMate XVE (Thoratec, CA) left ventricular assist device (LVAD) has two identical porcine valves, one for inflow and the other for outflow. The inflow valve endures a higher closing pressure than the outflow valve; thus, an implanted LVAD offers an ideal human model to study the independent effect of stress on calcification. Methods: Sixty-four pairs of LVAD inflow and outflow valves underwent gross examination, histologic study, and x-ray imaging. X-ray films were converted to digital images, and the calcification area was calculated. The distribution of calcium deposits was documented. The frequency and degree of calcification in both valves were analyzed (paired t test). Calcification of both valves in relationship to the duration of LVAD implantation and to the patient's age was also analyzed (linear regression). Results: The mean age of patients supported with LVAD was 55 ± 12 years (range, 17 to 77 years). The mean duration of LVAD implantation was 265 ± 151 days (range, 3 to 630 days). Calcification developed more commonly in inflow valves. The calcification area (CA) was larger in the inflow valves (21.6 ± 30.7 mm2) than in the outflow valves (15.1 ± 26.2 mm2, p < 0.05). There was a positive relationship between CA and days of implantation for both valves (inflow CA = 4.96 ± 0.063 days; outflow, CA = 2.39 ± 0.047 days, linear regression; p < 0.05 for both). Conclusions: Mechanical stress is an independent determinant of early bioprosthetic calcification in humans.