We assessed aspirin prophylaxis against venous thromboembolism in a prospective, controlled, double-blind study of patients over 40 years of age, who had undergone total hip replacement. Radiographic phlebography was the diagnostic end point. Thromboembolism developed in 11 of 44 patients receiving aspirin, as compared to 23 of 51 receiving the placebo (P less than 0.03). Unexpectedly, this protection was limited to men. In four of 23 men on aspirin thrombi developed, as compared to 14 of 25 receiving placebo (P less than 0.01). Corresponding figures for women were seven of 21 versus nine of 26. Review of a similar group of patients receiving aspirin revealed significantly greater protection (P less than 0.03) in men (three of 15) than in women (15 of 27). These data establish statistically significant prophylaxis in men over the age of 40 by 600 mg of aspirin given twice daily. The absence of a protective effect in women remains unexplained.