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Introduction: Non-vitamin K antagonist oral anticoagulants (NOACs) are fixed dose regimens indicated for stroke prevention in non-valvular atrial fibrillation (NVAF) patients. Dose adjustment is necessary in patients with renal insufficiency to optimize efficacy and safety.Objective: To assess NOAC dosing appropriateness and its effect on clinical outcomes in NVAF patients.Methods: Adult NVAF patients with ≥1 NOAC claim from 1/1/2013 to 12/31/2014, who were continuously enrolled for ≥12 months after index NOAC claim and had a documented creatinine clearance (CrCl) within 3 months before index date in the Optum/Humedica SmartFile™ database were eligible. NOAC dosage was classified as inappropriate or appropriate by level of renal function, age, and body weight per U.S prescribing information (USPI). Cox proportional models were used to assess the risks of bleeding and stroke associated with inappropriate NOAC dosing while adjusting for baseline characteristics.Results: Of the 388 eligible patients, 69 (17.8%) were inappropriately dosed. Rivaroxaban was the most commonly prescribed NOAC and had the highest inappropriate dosing rate (19.9% of 251 pts), followed by dabigatran (15.5% of 58 pts), and apixaban (12.7% of 79 pts). Most inappropriately dosed patients (73.9%) were under-dosed. Inappropriately dosed patients were older (p<0.0001), more likely to be female (p=0.008), had body weight ≤60kg (p=0.005), higher mean CHA2DS2-VASc scores (4.3 vs. 3.1, p<0.001), and higher mean Charlson Comorbidity Index (3.7 vs. 2.4, p<0.001). Inappropriately dosed patients had higher bleeding risk (15.9% vs. 5.6%, p=0.003) and similar stroke risk (7.2% vs. 5.3%, p=0.483) compared to appropriately dosed patients. Over-treated patients had a higher elevated risk of bleeding relative to appropriately dosed patients (HR=5.4, p=0.006) than under-dosed patients (HR=3.1, p=0.025). Risks of stroke for under-treated patients (HR=2.1, p=0.259) and over-treated patients (HR=0.6, p=0.690) were similar to appropriately dosed patients.Conclusion: Inappropriate dosing occurred in both patients with normal and insufficient renal function. Consideration of other factors beyond renal function is necessary to reduce bleeding risk associated with NOAC therapy.