OBJECTIVES: Rivaroxaban was shown to be effective in reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF) in a randomized controlled trial setting. The study objective was to assess real-world safety, effectiveness, and persistence of rivaroxaban and warfarin in nonvalvular AF patients.   METHODS: Healthcare claims from Symphony Health Solutions’ Patient Transactional Datasets from 5/2011-7/2012 were analyzed. Adult patients newly initiated on rivaroxaban or warfarin, with ≥2 AF diagnoses (ICD-9-CM: 427.31), and a CHADS2 score ≥1 during the 180-day baseline period were included. Cohorts were matched 1:4 using propensity score methods. Study outcomes were major bleeding, intracranial hemorrhage (ICH), gastrointestinal (GI) bleeding, composite stroke and systemic embolism, and venous thromboembolism (VTE) events (deep vein thrombosis [DVT] and pulmonary embolism [PE]). Cox proportional hazard models were used to compare event and persistence rates. RESULTS: The matched sample included 3,654 rivaroxaban and 14,616 warfarin patients. Matching was adequate, with all standardized differences in patient characteristics <10%. Mean age of both cohorts was 73 years; 51% were female. The mean (SD) drug exposure for the rivaroxaban and warfarin cohorts was 83 (58.0) and 114 (70.2) days, respectively. No significant differences were observed for bleeding, and the composite stroke and systemic embolism outcomes, although rivaroxaban users were associated with significantly fewer VTE events (hazard ratio [HR] = 0.46, 95% confidence interval [CI]: 0.23-0.91, p=0.0250) compared to warfarin users. Rivaroxaban was also associated with a significantly lower risk of treatment non-persistence (HR= 0.66; 95%CI: 0.60-0.72, p<0.001).  CONCLUSIONS: This analysis suggests that rivaroxaban and warfarin do not differ significantly in real-world rates of composite stroke and systemic embolism and major, intracranial, or GI bleeding. Rivaroxaban was associated with significantly fewer VTE events and better treatment persistence compared with warfarin.