Abstract Funding Acknowledgements Type of funding sources: None. Background Although current guidelines recommend the use of direct oral anticoagulants in patients with non-valvular atrial fibrillation (NVAF), the use of vitamin K antagonists (VKA) is still very widespread, especially in low to middle-income countries in Asia. If VKA/Warfarin is used, a target international normalized ratio (INR) range of 2.00-3.00 is recommended. Still, various studies conducted in Asia have found bleeding rates to be higher in this range. Thus, the "sweet spot" of INR targets in the Asian population is still under debate. Purpose This study aimed to compare bleeding and ischemic outcomes between the lower target INR and the standard target INR in an Asian population. Methods We conducted a systematic search in Pubmed, ScienceDirect, Cochrane, SinoMed, CNKI, and Wanfang data for studies conducted in East Asian countries comparing the outcome of standard INR targets (2.00-3.00) with lower INR targets in AF patients on VKA/Warfarin medication. The primary endpoints of interest are thromboembolic events and major bleeding. In addition, we performed a sub-analysis based on the lower INR with homogenized range (1.50-2.00) against the standard INR in primary outcomes. Secondary outcomes in this study were ischemic stroke, hemorrhagic stroke, minor bleeding, all-cause mortality, and treatment adherence. We used Review Manager 5.4 to calculate the result of 95% CI for the outcomes and odds ratios (OR). Results A total of 28 studies consisting of 10,533 patients from Japan, Korea, China, Hong Kong, and Thailand were included in our study. The incidence of thromboembolism was significantly higher in patients with a lower INR [OR 1.34 (95% CI 1.10-1.65; p=0.0005; I²=41%)], but if the lower INR was homogenized at range of 1.50–2.00 in the sub-analysis, there was no significant difference in events [OR 1.19 (95% CI 0.85-1.65; p=0.31; I²=0%)]. Major bleeding events [OR 0.36 (95% CI 0.28-0.46; p<0.00001; I²=0%)], hemorrhagic stroke [OR 0.24 (95% CI 0.14-0.42; p<0.00001; I²=0%)], and minor bleeding [OR 0.29 (95% CI 0.09-0.92; p=0.04; I²=0%)] was found to be significantly lower at the lower INR targets. Although there was no significant difference in all-cause mortality and ischemic stroke, a lower INR targets was associated with better treatment adherence in term of fewer patients discontinuing therapy independently [OR 0.48 (95% CI 0.28-0.48; p=0.007; I² =0%)]. Conclusion The incidence of bleeding was significantly higher in the Asian population treated with the standard target INR. Adjusting the lower target INR to 1.50-2.00 might be the sweet spot for the balance of ischemic and bleeding events to provide better outcomes in the Asian population with AF.