Chronic kidney disease (CKD) is a common comorbidity among patients taking direct-acting oral anticoagulants (DOACs). Herein, we evaluate the influence of kidney function on Stroke/SEE, hemorrhage and composite endpoints (Stroke/SEE/hemorrhage/death and Stroke/SEE/death) among patients on DOACs and warfarin. Baseline kidney function was categorized as GFR≥60 (reference), 45-59 and <45ml/min/1.73m for participants in the RE-LY (n=18,049), ARISTOTLE (n=18,187), and ENGAGE AF (n=20,798) trials. Incidence of events was compared across GFR categories. Hazard ratios for events was estimated using Cox regression using intention-to-treat analysis adjusting for known predictors. A large proportion of participants had GFR<60 (25-29% had GFR ≥45<60 and 9.5 to 12.6% with GFR <45). Compared to patients with GFR≥60, warfarin users across the trials with GFR≥45-59 and GFR<45 had a higher incidence of hemorrhage (p-values<0.0001) and warfarin users in the ARISTOTLE and ENGAGE trials had higher incidence of stroke/SEE (p-values ≤0.05). Compared to patients with GFR≥60, dabigatran users with GFR≥45-59 and GFR<45 had a higher incidence of stroke/SEE (p≤0.02), hemorrhage (p<0.001) and both composite endpoints (p<0.0001). Compared to patients with GFR≥60, apixaban and edoxaban users with GFR≥45-59 and GFR<45 had a higher incidence of hemorrhage (p-values≤0.05) and composite endpoints (p-values≤0.05). After adjustment, compared to patients with GFR≥60, warfarin users with GFR<60 in the ARISTOTLE and RELY trials had a higher risk of hemorrhage (p<0.05), as did dabigatran (p<0.001) and edoxaban (p≤0.005) users, while apixaban users did not exhibit an increased risk (p=0.08 GFR≥45-59; p=0.71 GFR<45). Kidney function significantly influences the safety and efficacy of oral anticoagulants.This article is protected by copyright. All rights reserved.