Postoperative infectious complications after breast surgery may result in significant morbidity, psychological trauma, and additional costs. We assessed the efficacy of preoperative antibiotic prophylaxis for surgery in a randomized, double-blind trial of 1,766 patients undergoing breast surgery. From January 1, 1996 to August 31, 1997, all eligible patients were assigned randomly to receive a single dose of ceftriaxone (2 g) or ceftazidime (2 g) given intravenously at the induction of anesthesia, with no further doses. The groups were similar with respect to age, operative procedure, operative time and time to discharge after operation. The patients who received ceftriaxone prophylaxis had 54. 4% fewer overall infections than those who received ceftazidime prophylaxis. Wound infection occurred in 0.45% of the ceftriaxone recipients (2 of 883) and 0.91% of the ceftazidime recipients (8 of 883). This prospective randomized double-blind study showed that the long-acting regimen containing ceftriaxone is more cost-effective than the short-acting ceftazidime in preventing postoperative infections in patients subjected to breast surgery.