OBJECTIVES: The introduction of non-vitamin K antagonist oral anticoagulants (NOACs) has been a major advance for stroke prevention in atrial fibrillation. Because NOACs have significant renal clearance, dose reduction is needed in patients with severe kidney disease. However, some physicians may prescribe reduced-dose NOACs to patients with relatively good renal function due to the concerns over the bleeding risk. We sought to investigate the use and clinical outcomes of reduced-dose NOACs in patients without severe renal impairment. METHODS: We performed a retrospective cohort analysis using a large U.S. commercial insurance database, OptumLabs Data Warehouse. We defined a renal indication for dose reduction as: dabigatran users with GFR <30 mL/min/1.73m, rivaroxaban users with GFR <50 mL/min/1.73m, and apixaban users with creatinine ≥1.5 mg/dL. Patients receiving reduced- and regular-dose NOACs were matched on socio-demographic characteristics, comorbidities, prior warfarin use and the use of concomitant P-gp and CYP3A4 inhibitors. Cox proportional hazard regression was used to compare the risk of stroke and major bleeding between patients received reduced- and regular-dose NOACs. RESULTS: We identified 12,593 patients with nonvalvular atrial fibrillation who received NOACs but did not have any renal indication for dose adjustment. 12.4% received a reduced dose (dabigatran: 8.2%; rivaroxaban: 14.9 %; apixaban: 15.4%). Older patients, females, and patients with higher stroke and bleeding risk at baseline were more likely to receive a reduced dose. In patients receiving dabigatran and apixaban, a reduced dose was associated with an increased risk of stroke (Hazard ratio [HR] 2.64 [1.01-6.89]), but little change in the risk of major bleeding (HR: 1.22 [0.67-2.23]). In patients receiving rivaroxaban, no relationship was observed between doses and the risk of stroke or major bleeding. CONCLUSIONS: Reducing dabigatran and apixaban doses in patients without severe renal impairment may be related to reduced effectiveness without any improvement in safety.