Introduction. Rivaroxaban is a new anticoagulant providing benefits for the treatment of patients with atrial fibrillation (AF). This study is aimed at evaluating the cost-effectiveness of rivaroxaban compared to warfarin in patients with AF. Method. This economic evaluation study was conducted among 144 selected nonrandomly patients who were treated with rivaroxaban or warfarin and suffered from AF leading to stroke, in the stroke ward of Shiraz Nemazee Hospital in 2019. The final and clinical (intermediate) outcomes were QALYs and no bleeding and prevention of ischemic stroke, respectively. The study was performed from the social perspective, and a deterministic one-way sensitivity analysis was conducted to identify the effects of uncertainty. The analysis of the collected data was carried out using SPSS18 and TreeAge software. Results. Patients who received rivaroxaban had lower costs ($ 25275 vs. $ 26554) and higher QALYs (0.5 vs. 0.33) compared to those taking warfarin. Bleeding and stroke occurred in (9 vs. 40) and (1 vs. 3) patients in the rivaroxaban and warfarin groups, respectively, and there was a significant decrease in the incidence of bleeding in the rivaroxaban group (81.9% vs 44.4%). Thus, rivaroxaban in all the outcomes was cheaper and more effective than warfarin. The one-way sensitivity analysis confirmed the robustness of the results. Conclusions. Considering the incremental cost-effectiveness ratio, rivaroxaban is more cost-effective and can be a dominant alternative. Therefore, it is suggested to use rivaroxaban as the first priority in AF patients because rivaroxaban reduces costs and increases clinical outcomes compared with warfarin.