BACKGROUND There is a paucity of evidence regarding the effects of non-vitamin K antagonist oral anticoagulants (NOACs) in underweight patients with atrial fibrillation (AF). OBJECTIVE The purpose of this study was to evaluate the efficacy and safety of NOACs in underweight AF patients. METHODS We analyzed 1353 AF patients who were prescribed NOACs according to their body mass index (BMI): underweight (UW: n = 62, BMI25.0 kg/m2). We analyzed the association between clinical outcomes and BMI. RESULTS During the median 7 months (interquartile range 3-10 months) of follow-up, there were 29 major bleeding events, 11 thromboembolic events, and 15 deaths. The risks of major bleeding and all-cause death were significantly higher in the UW group compared to the NW group (adjusted hazard ratio [HR] 4.135, 950/0 confidence interval [CI] 1.442-11.854, P =.008; adjusted HR 10.524, 95% CI 2.949-37.561, P < .001) and the OW group (adjusted HR 5.352, 95% CI 1.597-17.935, P = .007; adjusted HR 11.385, 95% CI 2.523-51.386, P = .002). However, there was no significant difference in the risk of thromboembolism among these groups. CONCLUSION In AF patients taking NOACs, being underweight was associated with an increased risk of major bleeding and all-cause death compared with being normal weight or overweight to obese, whereas the risk of thromboembolism was not different. Dose reduction should be considered in underweight patients who are at high risk for bleeding.