Objective: Data regarding the efficacy and safety of warfarin and Non-Vitamin K Antagonist Oral Anticoagulant (NOAC) among patients with chronic kidney disease (CKD) remain scarce. Methods: Systematic review and meta-analysis of studies involving CKD patients treated on OACs was conducted to evaluate following outcomes: ischemic stroke, intracerebral hemorrhage (ICH), combined ischemic and hemorrhagic stroke (strokecombined), stroke or systemic embolism, mortality, and major bleeding events. CKD was defined based on creatinine clearance (CrCl) ranging from mild (CrCl: 60-89 ml/min), moderate (CrCl: 30-59 ml/min) and severe (CrCl: 15-29 ml/min). Results: Fifteen studies (7 comparing NOAC vs. warfarin & 8 comparing warfarin vs. no anticoagulant) were identified comprising 87,291 patients. Warfarin (vs. no anticoagulant) was associated with reduced risk of ischemic stroke [RR=0.68 (95%CI: 0.55-0.84)] and mortality [RR=0.70 (95%CI: 0.62-0.78)]. In comparison to warfarin, NOAC use lowered the risk of ICH [RR=0.43 (95%CI: 0.33-0.56)], strokecombined [RR=0.83 (95%CI: 0.72-0.96)], stroke or systemic embolism [RR=0.73 (95%CI: 0.62-0.85)] and major bleeding [RR=0.77 (95%CI: 0.66-0.90)]. In adjusted analyses, warfarin use (vs. no anticoagulant) was associated with reduced mortality [HRadj=0.68 (95%CI: 0.61-0.76)], whereas NOAC (vs. warfarin) use reduced the risk of ICH [HRadj=0.39 (95%CI: 0.30-0.50)] and stroke or systemic embolism [HRadj=0.75 (95%CI: 0.65-0.88)]. Our sensitivity analyses comparing different NOACs exhibited that factor Xa inhibitors (compared to warfarin) consistently reduced strokecombined [RR=0.84 (95%CI: 0.73-0.96)], mortality [RR=0.84 (95%CI: 0.70-1.00)], ICH [RR=0.45 (95%CI: 0.24-0.85)] and major bleeding [RR=0.76 (95%CI: 0.64-0.91)]. Conclusions: Amongst CKD patients treated with OAC, NOACs present with a more favorable safety and efficacy profile for various cardiovascular outcomes.