Two antibiotic regimens for the prophylaxis of infection after colorectal operations were compared in a prospective, double blind, randomised controlled trial in 244 patients. Ninety-five patients (39%) were either excluded before randomisation or withdrawn, leaving 149 for analysis. Group 1 (n = 72) received a single infusion of 8 g fosfomycin and 1 g metronidazole at the induction of anaesthesia. Group 2 (n = 77) received bacitracin 250 mg plus neomycin 250 mg (as four tablets on three occasions over two days), metronidazole 500 mg tablets three times a day for one day, and ampicillin 1 g intravenously at induction of anaesthesia. Nine patients in group 1 (13%), 95% confidence interval (CI) 6.9 to 22.4, developed infective complications, compared with 8 in group 2 (10%), 95% CI 4.6 to 19.4. The overall infection rate was 17 of 149 evaluable patients (11%), 95% CI 6.8 to 17.7. Seven patients died (five in group 1 and 2 in group 2), two of whom (one in each group) died as a direct result of infective complications. Long operations and obesity were the most important risk factors, and may indicate a need for longer prophylaxis. Fosfomycin, which is mainly active against aerobic bacteria, was both safe and useful when combined with metronidazole.