This six-center, prospective, open-label clinical trial compared the efficacy and safety of three regimens recommended by the Centers for Disease Control and Prevention (CDC) for the treatment of women hospitalized for acute pelvic inflammatory disease (PID). The study focused on the response to inpatient therapy, not on long-term prevention of sequelae. A severity score was used for objective comparison of the degree of illness before and after therapy. Women were randomly assigned (in a 1:1:1 ratio) to treatment with cefoxitin plus doxycycline, clindamycin plus gentamicin, or cefotetan plus doxycycline. Two hundred seventy-five (94.2%) of 292 evaluable women required no alteration in therapeutic regimen. The three regimens produced almost identical cure rates. No serious adverse clinical or laboratory events were observed. In short, the three regimens recommended by the CDC for inpatient therapy of acute PID were similarly effective and safe.