This phase III, prospective, randomised, open, controlled clinical trial compared the efficacy of single-dose cefminox (2g) versus triple-dose cefoxitin (2g every 4 hours) as antibiotic prophylaxis in 112 women undergoing gynaecological surgery (vaginal or abdominal hysterectomy). Peak, intraoperative and trough serum concentrations were determined for both antibiotics, as well as their concentrations in myometrial tissue in a subset of patients from the study (22 patients from the cefminox group and 18 from the cefoxitin group). Clinical response was satisfactory in all women treated with cefminox (59 of 59) and in 52 of 53 patients treated with cefoxitin. Fever-related morbidity, hospital stay and adverse reactions were similar in both groups. Peak serum concentrations were 132.3 mg/L for cefminox and 82.2 mg/L for cefoxitin. 12-hour concentrations were 2.82 mg/L for cefminox and 2.17 mg/L for cefoxitin, and were higher than the respective minimum inhibitory concentrations (MICs) for pathogens commonly associated with this pathology. Uterine tissue concentrations were 24.5 and 41.6 mg/L for cefminox and cefoxitin, respectively, and also clearly exceeded MIC. It was shown that the use of a single preoperative dose of cefminox was similar in efficacy to 3 doses of cefoxitin administered every 4 hours, and that the serum and tissue concentrations attained provide adequate antibiotic coverage. In view of the general trend towards the use of a single dose for prophylaxis, cefminox offers a new alternative for antibiotic prophylaxis in gynaecological surgery.