Background: Atrial fibrillation (AF) is increasingly prevalent in chronic kidney disease (CKD) patients. The efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in AF and CKD patients remains unknown. This systematic review and meta-analysis will mainly assess net clinical benefit (NCB) property of NOACs versus warfarin in patients with AF and CKD by a pooled-analysis. Methods: We will search Medline, Embase, Cochrane Library, and Clinical Trials.gov Website comprehensively for eligible randomized controlled trials that report the efficacy and safety outcomes according to renal function of NOACs. Relative risks and their 95% confidence intervals will be calculated using fixed-and random-effects models. Subgroup, sensitivity, and regression analyses will be performed to evaluate intertrial heterogeneity and bias of the results. NCB that balance stroke/systemic embolism (SSE) and major bleeding will be calculated using Singer's method. Results: This systemic review and meta-analysis will evaluate the NCB of NOACs versus warfarin via SSE, major bleeding and all-cause death in patients with CKD. Conclusions: This study will provide new evidence for clinical profile of NOACs on SSE, major bleeding, all-cause death, and NCB in CKD patients. PROSPERO registration number: CRD42019116940.