Abstract Antibiotics used for prophylaxis in elective colorectal surgery should be effective against the organisms contaminating the soft tissues and isolated from postoperative infections. These are usually the enterobacteriaceae commensal to the colon. However, staphylococcal and anaerobic infections are not uncommon. Piperacillin has been used as antibiotic prophylaxis and been shown to be as efficacious as an aminoglycoside with metronidazole. Piperacillin is susceptible to many β-lactamases and we have therefore conducted a study to assess the efficacy of adding sulbactam, a β-lactamase inhibitor, to piperacillin for prophylaxis in elective colorectal surgery. Three hundred and seventy-nine patients were randomized to receive a single dose of piperacillin 4 g intravenously (iv) (group P, n = 192) or piperacillin 4 g with sulbactam 2 g iv (group SP n = 187). Fifty-three patients were withdrawn from analysis leaving 168 evaluable patients in group P and 158 patients in group SP. Postoperative infective complications occurred in 91 (28%) patients, 55 (33%) in group P and 36 (23%) in group SP ( X 2 = 4·0 P < 0·05). Surprisingly Staphylococcus aureus was isolated from wound infections in 22 patients (12 in group P and 10 in group SP) which represents 24% of those patients who developed infective morbidity. We conclude that sulbactam improves the efficacy of piperacillin as prophylaxis in elective colorectal surgery but does little to protect against staphylococcal wound infection.