It remains unclear whether non-vitamin K antagonist oral anticoagulants (NOACs) are more effective and safer than warfarin in low-weight patients with atrial fibrillation (AF). Here, we retrospectively compared the effectiveness and safety of NOACs with those of warfarin in low-weight patients with AF. We extracted the July 2011-September 2022 data of patients with AF treated with a NOAC (dabigatran, rivaroxaban, apixaban, or edoxaban) or warfarin at a tertiary hospital. The patients were divided into low-weight (body weight ≤ 60 kg) and non-low-weight (body weight = 60-100 kg) groups. The primary outcomes were hospitalization for ischemic stroke (IS) or systemic embolism (SE) and major bleeding, whereas the secondary outcomes were any ischemic and bleeding events. We used the inverse probability of treatment weighting to balance the baseline characteristics between the groups. In total, 5,044 patients (mean age = 73.7 years, mean CHA2DS2-VASc score = 3.0, mean HAS-BLED score = 2.3) were enrolled and divided into low-weight and non-low-weight groups-containing 1,666 (1,406 NOAC users, 260 warfarin users) and 3,378 (2,978 NOAC users, 400 warfarin users) patients, respectively. NOACs were associated with a lower risk of any bleeding event in the low-weight group (adjusted hazard ratio = 0.61, 95% confidence interval = 0.51-0.73). The between-group differences in the risks of IS/SE, any ischemic event, major bleeding, and any bleeding event were nonsignificant. Thus, the use of NOACs (specifically dabigatran or edoxaban) is associated with a lower risk of any bleeding event than warfarin use in low-weight patients with AF.