Adult patients with acute sinusitis (n = 236) were randomized in a double-blind study to levofloxacin 500 mg orally once daily (n = 119) or clarithromycin 500 mg orally twice daily (n = 117) for 10-14 days. Between 2 and 5 days after therapy participants were evaluated as cured (no symptoms), improved (symptoms improved, no further therapy required), or failed (further therapy required). Clinical response rates (cured plus improved) for clinically evaluable patients were 93.9% for levofloxacin (n = 98) and 93.5% for clarithromycin (n = 93). The proportion of patients evaluated as cured was higher in the levofloxacin (40.8%) than in the clarithromycin arm (29.0%) and individual symptoms showed higher rates of resolution. Of patients receiving levofloxacin and clarithromycin, 22.5% and 39.3%, respectively, experienced adverse events related or possibly related to the study therapy. This study showed that, in the treatment of acute sinusitis, daily levofloxacin therapy is as effective as twice-daily clarithromycin therapy with more complete clearing of symptoms and a more tolerable side-effect profile.