Hemolytic anemia is a relatively common complication after the replacement of cardiac valves with mechanical prostheses; the prevalence rate varies from 38% to 85%, depending on the prosthesis implanted. However, cardiac valves fabricated from biologic material are associated with a reduced incidence of hemolytic anemia, and to the authors' knowledge this report is the first to document hemolytic anemia in a patient who had the mitral valve replaced with an Ionescu-Shiley valve. The anemia was not associated with evidence of hemodynamically important mitral regurgitation and was ultimately controlled by iron and folate supplements.