Community-acquired pneumonia remains a significant health concern despite the availability of effective antibiotics. This randomized, double-masked, double-dummy, multicenter comparative trial was undertaken to compare the efficacy and safety of sparfloxacin with those of clarithromycin in the treatment of community-acquired pneumonia. In 54 centers throughout the United States, 342 patients aged > or = 18 years with community-acquired pneumonia were enrolled in this trial. A total of 167 patients, 98 males and 69 females with a mean age of 51.0 years (range, 18-87), received a 400-mg loading dose of sparfloxacin on the first day, followed by 200 mg once daily for a total of 10 days. A total of 175 patients, 85 males and 90 females with a mean age of 51.3 years (range, 18-91), received clarithromycin 250 mg twice daily for 10 days. In the intent-to-treat population, 133 (79.6%) patients in the sparfloxacin group and 145 (82.9%) in the clarithromycin group were cured or improved (the 95% confidence interval [CI] for the differences in success rate between sparfloxacin and clarithromycin was -11.5% to 5.1%). Success rates for the per-protocol patients were 88.7% (133/150) in the sparfloxacin group and 88.9% (144/162) in the clarithromycin groups (95% CI, -7.2% to 6.8%). There were no significant differences in success rate between treatment groups based on age > or = 65 years. The overall bacteriologic response rates in the bacteriologically assessable population were 97.0% (64/66 isolates) in the sparfloxacin group and 91.4% (74/81 isolates) in the clarithromycin group. Recurrence occurred in 6.0% of per-protocol patients in the sparfloxacin group and 6.3% of patients in the clarithromycin group. The overall frequency of adverse events was 56.3% in the sparfloxacin group and 65.1% in the clarithromycin group. Gastrointestinal disturbances were the most common adverse event in both groups. Abnormal taste related to study drug was reported by 17 patients (9.7%) treated with clarithromycin, versus 3 patients (1.8%) treated with sparfloxacin (P = 0.002). Photosensitivity reactions were reported in 10 patients (6.0%) treated with sparfloxacin, versus 1 patient (0.6%) treated with clarithromycin (P = 0.002). QT-interval prolongation was documented in 4 patients (2.4%) in the sparfloxacin group and no patients in the clarithromycin group. Thus sparfloxacin was as well tolerated and as effective as clarithromycin in the treatment of community-acquired pneumonia.