OBJECTIVE: Chronic rhinosinusitis (CRS) is one of the most prevalent and costly diseases in the US; approximately 27.9 million antibiotic prescriptions were dispensed for CRS treatment in 2001. Little is known about the treatment, costs, and outcomes for patients with CRS. The purpose of this study was to compare two therapies, moxifloxacin and levofloxacin, for CRS focusing on real-world treatment practices, outcomes, and charges. METHODS: A retrospective analysis of the Pharmetrics US claims database was conducted on patients who initiated CRS treatment with moxifloxacin or levofloxacin between April 2000 and March 2002 (N=1579). Definitions were developed a priori for CRS treatment episodes and durations along with measures of treatment failure and recurrence. Costs were calculated by summing all charges incurred during each CRS episode, applying a natural log transformation. Ordinary least squares, logistic, and proportional hazard regression models were used to compare groups, controlling for other explanatory variables. RESULTS: The treatment groups were similar in demographic characteristics. As expected (due to label recommendation differences) moxifloxacin was typically used for a shorter duration of time than levofloxacin: 2.18 fewer days for the original prescription for the episode (p<0.0001) and 2.11 fewer total days of monotherapy per episode (p<0.0001). Despite the shorter durations, the outcomes of treatment were similar for both groups. Moxifloxacin demonstrated a lower probability of any recurrence (p<0.0001). However, the outcome measures of chronic sinusitis recurrence and odds of treatment failure were not significantly different between groups. In addition, lower average log charges (p<0.0001) resulted for the moxifloxacin-treated group. CONCLUSIONS: Moxifloxacin demonstrated significantly shorter therapy duration and lower charges with similar outcomes to levofloxacin in a real-world comparison. This study demonstrates that moxifloxacin is an excellent treatment option when a fluoroquinolone is indicated for the treatment of an acute exacerbation of CRS.