BACKGROUND To compare amoxicillin-clavulanic acid with cefazolin as ultra-short-term prophylaxis in laparotomic gynecologic surgery. METHODS A prospective randomized study was conducted to compare two antimicrobial regimens in surgical prophylaxis of laparotomic surgery. Patients were randomly allocated to receive amoxicillin-clavulanic acid (2.2 g) [Group A] or cefazolin (2 g) [Group B] as a single dose 30 min before surgery. Each patient was assessed daily until discharge to evidence febrile status and the presence of infections at the operative site, urinary tract, and respiratory tract. RESULTS In the amoxicillin-clavulanic acid (Group A) and cefazolin (Group B) groups, overall 346 and 352 patients, respectively, were evaluable for prophylactic efficacy at hospital discharge. Infectious complications were infrequent in both arms. Febrile morbidity occurred in 21 (6.1%) and 26 (7.4%) patients, respectively, in the amoxicillin-clavulanic acid and cefazolin groups. Wound infection and urinary tract infection were also higher, but not significantly in the cefazolin group (0.5% vs. 1.1% and 2.0% vs. 2.5%, respectively). There was one respiratory tract infection (0.2%) in Group B, and no septic death in either groups. CONCLUSIONS Ultra-short-term prophylaxis with both amoxicillin-clavulanic acid and cefazolin is safe in elective laparotomic gynecologic surgery.