OBJECTIVES: Acute sinusitis (AS) is a common infection, with over 20 million cases occurring annually in the US. The purpose of this study was to compare real-world use of two fluoroquinolones, moxifloxacin and levofloxacin, for treatment of AS and resulting outcomes and charges. METHODS: A retrospective analysis of the Pharmetrics claims database was conducted identifying patients who initiated AS treatment with moxifloxacin or levofloxacin between April 2000 and March 2002 (N=4880). Definitions were developed a priori for AS treatment episodes and duration along with measures of AS treatment failure and recurrence. Costs were calculated by summing all per-patient charges incurred during the treatment episodes, applying a natural log transformation. Ordinary least squares, logistic, and proportional hazard regression models were used to compare groups, controlling for covariates. RESULTS: Treatment groups had similar demographic characteristics. As expected (due to differences in label recommendations) moxifloxacin was used for a shorter duration of time than levofloxacin: 1.65 fewer days for the original prescription per episode (p<0.0001) and 2.06 fewer total days of monotherapy per episode (p<0.0001). Despite the shorter duration, moxifloxacin performed significantly better than levofloxacin on outcomes with a 35% lower probability of recurrence (p<0.0001) and 26% lower odds of treatment failure (p<0.0001). In addition, lower average log charges (p<0.0001) resulted for the moxifloxacin-treated group. CONCLUSIONS: In keeping with guideline recommendations, fluoroquinolones are indicated when patients present with moderate acute sinusitis, or mild acute sinusitis and have recently taken antibiotics. In selecting a fluoroquinolone, it is helpful for clinicians to consider 'real-world' effectiveness. In this study, the moxifloxacin group experienced better outcomes than the levofloxacin group, with a significantly lower probability of recurrence or treatment failure, even with a shorter duration of therapy. This study demonstrates moxifloxacin is an excellent treatment option when a fluoroquinolone is indicated for acute sinusitis.