The International Society of Thrombosis and Haemostasis recommends warfarin therapy over direct oral anticoagulants (DOACs) in patients with a body mass index >40 kg/m2 or weight > 120 kg due to limited clinical data in morbidly obese patients. The aim of the meta-analysis was to compare DOACs with warfarin in morbidly obese patients with atrial fibrillation (AF) and to optimize an anticoagulation therapy in the population. MEDLINE, Embase, Google Scholar, Web of Science, and Cochrane Library database searches for relevant articles through December 23, 2019 were performed. Total 5 studies for the event rate of stroke or systemic embolism (SE) and 4 studies for major bleeding were included in the meta-analysis. It showed that there was no statistically significant difference in stroke or SE event rate between the DOAC and warfarin groups (odds ratio: 0.85; 95% confidence interval: 0.60, 1.19; p = 0.35; I2 = 0 %). The DOAC use was significantly associated with a lower major bleeding event rate compared the warfarin group (odds ratio: 0.63; 95% confidence interval: 0.43, 0.94; p = 0.02; I2 = 30%). In conclusion, DOACs should be considered as an oral anticoagulant for preventing stroke or SE in morbidly obese patients with AF. A randomized controlled trial comparing a DOAC with warfarin is needed to confirm our meta-analysis results in morbidly obese patients with AF.