Abstract The efficacy of single-dose cefminox versus multiple-dose cefoxitin as antimicrobial prophylaxis in surgical treatment for colorectal cancer was compared in a prospective, randomized, single-masked, Phase III clinical trial. A total of 124 patients were entered into the study, and 31 were withdrawn after randomization. Of the 93 assessable patients, 47 received cefminox (2 g intravenously at induction of anesthesia) and 46 received cefoxitin (2 g intravenously at induction of anesthesia with subsequent doses 4 and 8 hours later). The incidence of postoperative infectious complications was similar in both groups: wound infection, 5 patients (10.6%) with cefminox and 3 (6.5%) with cefoxitin; intra-abdominal infection, 1 (2.1%) in the cefminox group and 1 (2.2%) in the cefoxitin group. Adverse events were few, and we found no statistical difference between antibiotic regimens. We concluded that single-dose cefminox 2-g monotherapy offers good prophylaxis in elective colorectal surgery. In this setting, cefminox is as effective as cefoxitin 6 g (2 g/4 h).