In a primary care setting, the efficacy and safety of ciprofloxacin (CIP) 500 mg b.i.d. were compared with those of cefuroxime axetil (CA) 250 mg b.i.d., each given for 10 days, in a nationwide, open, prospective, randomized trial of 1414 adults with acute sinusitis. Patients were enrolled if they had clinically documented acute sinusitis (ie, rhinosinusitis) (<4 weeks' duration), based on the 1997 American Academy of Otorhinolaryngology--Head and Neck Surgery criteria of either two major or one major and two minor symptoms. The primary efficacy variable was clinical response (resolution or failure) at the posttherapy assessment on study days 14 through 26. The most common presenting major signs and symptoms of acute rhinosinusitis were facial congestion, nasal drainage/purulence, facial pain/pressure, and nasal obstruction/blockage. The minor symptom, headache, was more common and severe than was nasal obstruction/blockage. A total of 1219 patients were clinically evaluable. Clinical resolution was observed in 559 of 613 (91.2%) CIP-treated patients and 546 of 606 (90. 1%) CA-treated patients. The two regimens were statistically equivalent (95% confidence interval, -2.16% to 4.71%). There were 80 drug-related adverse events reported in the CIP-treated patients and 81 drug-related adverse events reported in the CA-treated patients. The main adverse events were nausea (n = 18) and diarrhea (n = 7) in patients treated with CIP and diarrhea (n = 14), nausea (n = 12), headache (n = 7), and vaginitis (n = 7) in those treated with CA. CIP 500 mg b.i.d. was found to be statistically equivalent to CA 250 mg b.i.d. in the treatment of acute rhinosinusitis.