Background and objective: the study analysed the effectiveness and safety of warfarin use compared with warfarin nonuse and non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients aged >= 65 years. Methods: after searching PubMed and the Cochrane Library, 26 studies were included, with 10 comparing warfarin with warfarin non-use and 16 comparing warfarin with NOACs, in older AF patients (>= 65 years). Results: warfarin use was superior to no antithrombotic therapy [relative risk (RR) 0.59, 95% confidence interval (CI) 0.51-0.76, I-2 = 12.3%, n = 8] and aspirin (RR 0.44, 95% CI 0.24-0.64, I-2 = 0.0%, n = 5) for stroke/thromboembolism (TE) prevention. Warfarin use was associated with a non-significant increase in risk of major bleeding compared with no antithrombotic therapy (RR 1.26, 95% CI 0.99-1.52, I-2 = 0.0%, n = 7) and aspirin (RR 1.20, 95% CI 0.91-1.50, I-2 = 0.0%, n = 5). NOACs were superior to warfarin for stroke/TE prevention [hazard ratio (HR) 0.81, 95% CI 0.73-0.89, I-2 = 56.6%, n = 9], and also were associated with reduced risk of major bleeding compared to warfarin (HR 0.87, 0.77-0.97, I-2 = 86.1%, n = 9). Conclusions: warfarin use was superior to warfarin non-use, aspirin and no antithrombotic therapy in reducing the risk of stroke/TE in older AF patients, but with a possible increase in major bleeding. NOACs were superior to warfarin for stroke/TE prevention, with reduced risk of major bleeding.