OBJECTIVE To evaluate the efficacy and safety of ampicillin/sulbactam with those of clindamycin/gentamicin. METHODS A prospective, randomized clinical trial of patients with the diagnosis of postpartum endometritis. Intravenous ampicillin, 2.0 g, combined with 1.0 g sulbactam was administered every six hours or intravenous clindamycin, 900 mg, plus gentamicin, 1.5 mg/kg (not to exceed 150 mg unless gentamicin levels were obtained) every eight hours. Endometrial and blood specimens were obtained for culture and antibiotic susceptibility testing. RESULTS One hundred twenty-nine hospitalized women with the diagnosis of endometritis were enrolled. Both treatment regimens were equally effective. At the end of treatment, 42 of 51 (82%) ampicillin/sulbactam-treated patients achieved clinical cure in comparison to 47 of 56 (84%) patients in the clindamycin/gentamicin group. Respective bacterial eradication rates of 86% and 84% for each treatment group were seen. Both antibiotic regimens were well tolerated, with no statistically significant difference in the incidence of adverse experiences. CONCLUSIONS The two antibiotic regimens were equally effective for a clinical cure, bacterial eradication and incidence of adverse experiences.