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Introduction and Objectives: The efficacy and safety of ticagrelor vs prasugrel in patients with acute coronary syndromes (ACS) according to body mass index (BMI) remain unstudied. We assessed the efficacy and safety of ticagrelor vs prasugrel in patients with ACS according to BMI., Methods: Patients (n=3987) were grouped into 3 categories: normal weight (BMI <25kg/m 2 ; n=1084), overweight (BMI ≥ 25 to <30kg/m 2 ; n=1890), and obesity (BMI ≥ 30kg/m 2 ; n=1013). The primary efficacy endpoint was the 1 year incidence of all-cause death, myocardial infarction, or stroke. The secondary safety endpoint was the 1 year incidence of Bleeding Academic Research Consortium type 3 to 5 bleeding., Results: The primary endpoint occurred in 63 patients assigned to ticagrelor and 39 patients assigned to prasugrel in the normal weight group (11.7% vs 7.5%; HR, 1.62; 95%CI, 1.09-2.42; P=.018), 78 patients assigned to ticagrelor and 58 patients assigned to prasugrel in the overweight group (8.3% vs 6.2%; HR, 1.36; 95%CI, 0.97-1.91; P=.076), and 43 patients assigned to ticagrelor and 37 patients assigned to prasugrel in the obesity group (8.6% vs 7.3%; HR, 1.18; 95%CI, 0.76-1.84; P=.451). The 1-year incidence of bleeding events did not differ between ticagrelor and prasugrel in patients with normal weight (6.5% vs 6.6%; P=.990), overweight (5.6% vs 5.0%; P=.566) or obesity (4.4% vs 2.8%; P=.219). There was no significant treatment arm-by-BMI interaction regarding the primary endpoint (P int =.578) or secondary endpoint (P int =.596)., Conclusions: In patients with ACS, BMI did not significantly impact the treatment effect of ticagrelor vs prasugrel in terms of efficacy or safety., Clinical Trial Registration: NCT01944800., (Copyright © 2021 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)