We evaluated vasectomy as a potential risk factor for urolithiasis. Vasectomy is a common method of contraception among otherwise healthy men. This is also the population at highest risk for urolithiasis. We conducted a case-control study of patients in a large prepaid health maintenance organization. Cases were men experiencing initial episodes of urolithiasis, ascertained by reviewing radiology logs and medical records. The age-matched controls were men with no history of urolithiasis. In logistic regression models, the relative risk of urolithiasis for men with vasectomies compared with men without vasectomies was 1.9 for men younger than 46 years of age (95% confidence interval = 1.2 to 3.1, P = 0.005), and the relative risk was 0.9 (95% confidence interval = 0.5 to 1.5, P > 0.8) for men who were at least 46 years old. The relative risk of urinary calculi was 2.0 (95% confidence interval 1.0 to 4.1, P < 0.05) for men with vasectomies 0 to 4 years before evaluation compared with men without vasectomies, and the excess risk persisted as long as 14 years postvasectomy. Vasectomy was associated with a twofold increased risk for urolithiasis in men younger than 46 years of age. This increased risk may persist for up to 14 years postvasectomy. Given the large number of men who undergo vasectomy worldwide each year, the increased risk for urolithiasis among vasectomized men may result in substantial excess morbidity.