The objective of the study was to compare the efficacy of azithromycin, alone or with metronidazole, versus two standard multidrug regimens for the treatment of acute pelvic inflammatory disease (PID). Patients with PID were treated with once-daily intravenous (i.v.) azithromycin 500 mg for 1 day or 2 days followed by once-daily azithromycin 250 mg orally for a total of 7 days, alone or with three-times-daily metronidazole 400 mg or 500 mg i.v. then orally for a total of 12-14 days. The comparators were either metronidazole + doxycycline + cefoxitin + probenecid or doxycycline + amoxycillin/clavulanate given at standard recommended doses for up to 21 days. In total, 309 patients were treated for PID. The diagnosis was confirmed laparoscopically in 74.8% of patients. Rates of clinical success for azithromycin, alone (97.1%) or with metronidazole (98.1%), were comparable to those for the comparator regimens (94.6%). Eradication rates for Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma hominis and anaerobes were also comparable for each of the treatment groups. Both azithromycin regimens were well tolerated. In conclusion, azithromycin, alone or with metronidazole, provides a shorter, simpler treatment option for the successful management of acute PID.