Objective:To evaluate the efficacy and safety of ampicillin‐sulbactam (3 g every 6 hours) in patients with pelvic inflammatory disease or postpartum endometritis using a randomized, comparative, multicenter study of parallel design.Methods:Eligible patients with pelvic inflammatory disease were randomized to receive either ampicillin‐sulbactam or cefoxitin (2 g every 6 hours) plus doxycycline (100 mg every 12 hours). Those with endometritis were randomized to ampicillin‐sulbactam or clindamycin (900 mg every 8 hours) plus gentamicin (1.5 mg/kg every 8 hours). In the ampicillin‐sulbactam group, chlamydia‐positive patients also received oral doxycycline.Results:For pelvic inflammatory disease, the clinical response rates (cure or improvement) were 85.5% (47 of 55) and 89.6% (43 of 48) in the ampicillin‐sulbactam and cefoxitin and doxycycline groups, respectively (X2= 0.10,P= .76). For endometritis, the clinical response rates were 88.7% (141 of 159) and 90.8% (139 of 153) in the ampicillinsulbactam and clindamycin and gentamicin groups, respectively (X2= 0.15,P= .70). The percentages of patients with pelvic inflammatory disease who had adverse experiences were not significantly different in the cefoxitin and doxycycline group (47% [29 of 62]) than in those receiving ampicillin‐sulbactam (33% [22 of 66]) (P= .12). These adverse effects were mostly mild or moderate. In the endometritis subjects, the incidence of adverse experiences in the ampicillin‐sulbactam group (11% [20 of 179]) was comparable to that during treatment with clindamycin and gentamicin (12% [22 of 180]). These adverse experiences were also mostly mild to moderate.Conclusion:Ampicillin‐sulbactam is as effective and well tolerated as combination regimens using cefoxitin plus doxycycline and clindamycin plus gentamicin for the treatment of pelvic inflammatory disease or endometritis, respectively.(Obstet Gynecol 1994;83:998‐1004)