The effectiveness of perioperative antibiotic prophylaxis against wound infections following breast surgery was investigated by meta-analysis of published data from a randomized clinical trial and an observational data set, which included a total of 2587 surgical procedures, including excisional biopsy, lumpectomy, mastectomy, reduction mammoplasty and axillary node dissection. There were 98 wound infections (3.8%). Prophylaxis was used for 44% (1141) of these procedures, cephalosporins accounted for 986 (86%) of these courses of antibiotics. Prophylaxis prevented 38% of infections, after controlling for operation type, duration of surgery and participation in the randomized trial (Mantel-Haenszel Odds Ratio = 0.62, 95% confidence interval = 0.40-0.95, P = 0.03). There was no significant variation in efficacy according to operation type or duration. We conclude that antibiotic prophylaxis significantly reduces the risk of postoperative wound infection following these commonly performed breast procedures.