Results of two recent prospective incidence studies have suggested that certain subgroups ot men with diabetes mellitus may be protected from developing prostate cancer. Two earlier studies, however, concluded that diabetes increased the risk of mortality from prostate cancer. With hundreds of thousands of male respondents, the 1959–1972 Cancer Prevention Study provided a unique opportunity to explore whether men with diabetes were more likely to develop prostate cancer during a 13-year follow-up period than were men without diabetes. After adjusting for factors associated with prostate cancer in previous studies, we found little association between diabetes at baseline and prostate cancer incidence [incidence density ratio (IDR) = 1.05; 95% confidence interval (CD = 0.81–1.36]. Men who had diabetes mellitus for 5 or more years, however, had a higher incidence of prostate cancer than did men without diabetes (IDR = 1.56; 95% CI = 1.02–2.38). Among all study participants who were diagnosed with prostate cancer, men with diabetes were only slightly more likely to die from prostate cancer than were men without diabetes (IDR = 1.11; 95% CI = 0.76–1.62). (Epidemiology 1999;10:313–318)