OBJECTIVES: To examine treatment failure rates, disease-related medical complications and healthcare costs among CAP outpatients treated with levofloxacin (LEVO) or amoxicillin/ clavulanate (AC). METHODS: Using adjudicated, commercial health insurance claims data (PharMetrics, Inc.), patients with an outpatient CAP diagnosis between July 2003 and December 2004, aged 18–64, with 6-months enrollment pre– and post–diagnosis, receiving LEVO or AC monotherapy within 3 days of diagnosis, were identified. Patients with recent hospitalization (10 days), prior antibiotic therapy (30 days), or immunocompromised state were excluded. Treatment failure was defined as receipt of a renewal or alternative antibiotic claim, or hospitalization 28 days post–prescription claim. Complications and infection related costs were tracked for 6-months post–diagnosis. Demographic, clinical, pre–index utilization, and study endpoints were evaluated via descriptive, univariate (Wilcoxon and Chi-Square tests for continuous and dichotomous variables, respectively) and multivariate techniques (logistic regression for treatment failure and complications, General Linear Model for costs). RESULTS: Of 4030 LEVO and 951 AC patients analyzed, the cohorts had similar demographic and clinical profiles (pre–diagnosis utilization and cost, comorbidity burden, Charlson score), except age (LEVO vs AC: 45.8 vs. 42.7 y, p<0.001), gender distribution (females 49.5% vs. 53.4%, p<0.001), and asthma prevalence (4.9% vs 6.8%, p=0.017). The AC group had a higher percentage (22.0% vs. 18.5%, p=0.015) and likelihood (OR=1.27, 95% CI 1.07–1.52, p=0.007) of treatment failure than the LEVO group. The rates of infection–related complications were 8.6% for LEVO and 8.2% for AC; (OR 1.12, 95% CI 0.80–1.56, p=0.52). No difference was observed in infection–related costs (mean ± SD: LEVO $1067 ± 3562 vs. AC $1159 ± 5874). CONCLUSION: LEVO and AC groups were comparable. The LEVO group experienced significantly lower treatment failure, but no significant differences in complications or costs, compared to the AC group, in outpatient CAP.