First-generation prosthetic heart valves commonly caused sufficient red blood cell (RBC) injury to induce hemolytic anemia. Although multiple studies have shown that new-generation valves are not associated with anemia, the extent to which these valves are injurious to RBCs is not known, because RBC survival not has not been measured in these subjects. Using a technique that uses breath carbon monoxide (CO) to quantify RBC turnover, this study measured RBC life span in 38 subjects with normally functioning, new-generation valves. Erythrocyte survival averaged 98.8 ± 23 and 103 ± 15 days, respectively, in 20 subjects with mechanical valves and 18 subjects with bioprosthetic valves (p >0.05). However, these life spans were significantly (p <0.01) less than those of healthy subjects (122 ± 23 days) and a group of elderly subjects with osteoarthritis (128 ± 26 days). The mean hemoglobin concentrations of the 2 groups of valve patients were within normal limits. In conclusion, new-generation heart valves commonly are associated with a small degree of hemolysis that is compensated for by increased RBC production.