Background The efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndromes (ACS) according to body mass index (BMI) remain unknown. Purpose To assess the efficacy and safety of ticagrelor versus prasugrel in patients with ACS according to BMI. Methods This post-hoc analysis of the ISAR-REACT 5 trial included 3987 patients with BMI data available. BMI was grouped in 3 categories: low (BMI Results There was no significant treatment arm-by-BMI interaction regarding the primary endpoint (Pint=0.578). However, the primary endpoint occurred in 63 patients assigned to ticagrelor and 39 patients assigned to prasugrel in the low BMI group (11.7% vs. 7.5%; hazard ratio [HR]=1.62; 95% confidence interval [CI], 1.09–2.42; P=0.018), 78 patients assigned to ticagrelor and 58 patients assigned to prasugrel in the intermediate BMI group (8.3% vs. 6.2%; HR=1.36 [0.97–1.91]; P=0.076), and 43 patients assigned to ticagrelor and 37 patients assigned to prasugrel in the high BMI group (8.6% vs. 7.3%; HR=1.18 [0.76–1.84]; P=0.451). BARC type 3 to 5 bleeding events did not differ between ticagrelor and prasugrel in patients with low (6.5% vs. 6.6%), intermediate (5.6% vs. 5.0%), or high (4.4% vs. 2.8%) BMI. Conclusions BMI of patients with ACS did not impact significantly on the treatment effect of ticagrelor vs. prasugrel in terms of both efficacy and safety. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): German Center for Cardiovascular Research;Deutsches Herzzentrum München, Germany