To compare the efficacy, safety, and tolerability of intravenous moxifloxacin with those of a commonly used empirical antibiotic regimen, cefoperazone and azithromycin in the treatment of community acquired pneumonia (CAP) in adult patients requiring initial parenteral therapy, 40 patients with CAP were divided into two groups, a moxifloxacin group (n = 20) and a control group (n = 20), which were treated for 7 to 14 days. The patients in the moxifloxacin group were intravenously given 400 mg of moxifloxacin (Avelox) once a day. Patients in the control group were administered 2.0 g of cefoperazone twice a day and azithromycin 0.5 g once a day. Clinical, bacteriological, and laboratory examinations were performed before the treatment, and at the end of the treatment. Our results showed that there was no significant difference in the clinical efficacy rate between two treatment groups at end of therapy (90% for moxifloxacin, 95% for cefoperazone plus azithromycin) (P > 0.05). The bacteriologic eradication rate at the end of treatment was 90% in the moxifloxacin group and 80% in the cefoperazone-plus-azithromycin group, whereas there was no significant difference between the two groups (P > 0.05). In addition, both drugs were well-tolerated in this trial, with the number of drug-related adverse events being comparable. It is concluded that moxifloxacin is an effective and well-tolerated treatment for CAP and was equivalent to the commonly used empirical treatment of cefoperazone plus azithromycin. Moxifloxacin is likely to offer clinicians an alternative for reliable empirical CAP treatment in the face of increasing antibiotic resistance.