Autologous blood donations may provide a new source of blood when components not used by the donors are deemed suitable for homologous use. However, the risk of transfusion-transmitted diseases form such donors has not been evaluated. We compared the prevalence of infectious markers and rate of abnormal responses to a confidential donor ballot in autologous donors from two blood collection programs, one blood center and one hospital-based, to corresponding homologous blood programs. The incidence of abnormal test results in autologous donors for HIV antibodies (either Western blot confirmed or repeatedly reactive, unconfirmed), HBsAg, ALT, and anti-HBc were not statistically different from homologous rates. The incidence of STS abnormalities in autologous donors was statistically significant, although all positive results were biologic false positives. The rate of abnormal responses to the confidential ballot was statistically significant only in autologous donors whose collections were already determined to be unsuitable for homologous use due to medical history problems. Although the data do not address infectious complications in transfusion recipients, this study offers no evidence that autologous blood components are less safe than their homologous equivalents.