Seventy-seven patients who had elective pulmonary resections were enrolled in a prospective double-blind study to assess the role of prophylactic antibiotics in preventing postoperative infections. Criteria for infection were strictly defined. A five-day course of a cephalosporin (2 gm/day in divided doses) was compared to an identical placebo. There were 17 infections in the 34 patients in the placebo group (50%), compared to only eight infections in the 43 patients in the antibiotic group (19%) (P = .005). When infections unrelated to thoracotomy and minor infections were excluded, the advantage of prophylactic antibiotics proved even more evident. Fourteen thoracic infections occurred in the placebo group (41%) compared to only two thoracic infections (4.7%) in the antibiotic group (P = .0002). No relationship of infection rate to the extent of pulmonary resection was found. A history of smoking, the presence or absence of chronic bronchitis, spirometric abnormalities, and obesity were all analyzed; none was related to the development of infection. We conclude that the routine use of perioperative antibiotics is indicated to prevent postoperative infections in pulmonary resection.