To examine the relationship between vasectomy and prostate cancer.Retrospective cohort study.Husbands of nurses in 11 large states in the United States.In questionnaires administered in 1976 and 1978, 14,607 married female participants of the Nurses' Health Study reported vasectomy as the couple's form of contraception. In 1989, we contacted these 14,607 women and 14,607 age-matched participants whose husbands had not had a vasectomy prior to 1978 to ascertain their husband's disease status between 1976 and 1989.Diagnosis of prostate cancer.During the study period, from 1976 through 1989, 96 new cases of prostate cancer were diagnosed in the cohort. Vasectomy was associated with an increased risk of prostate cancer (age-adjusted relative risk, 1.56; 95% confidence interval, 1.03 to 2.37; P = .04). The relative risk of prostate cancer increased over time since vasectomy. Among men who had their vasectomy 20 or more years in the past, the relative risk of prostate cancer was 1.89 (95% confidence interval, 1.14 to 3.14; P = .005), and after excluding stage A and B cases, the relative risk was 2.06 (95% confidence interval, 0.95 to 4.43; P = .07). This elevated risk of prostate cancer among vasectomized men persisted when we adjusted for smoking, alcohol consumption, educational level, body mass index, and geographical area of residence.These results support evidence from other epidemiologic studies that vasectomy increases risk of prostate cancer. A biological mechanism whereby vasectomy influences the rate of prostate cancer may be related to a diminished secretory rate of prostatic fluid following vasectomy, or, alternatively, to the postvasectomy immune response to sperm antigens, which may cross-react with tumor-associated antigens and suppress tumor immunosurveillance mechanisms.