We evaluated the impact of triple antiplatelet therapy on platelet reactivity, reducing cardiovascular events and the safety in obese patients undergoing coronary stenting. Obese patients (n = 428) undergoing coronary stenting were randomly assigned to 2 groups: standard dual group (clopidogrel plus aspirin, n = 215) and triple group (n = 213); adjunctive cilostazol was added to the dual group treatment. Platelet reactivity was assessed at baseline and at 1-year follow-up by conventional aggregometry. Major adverse cardiovascular events, stent thrombosis, target lesion revascularization (TLR), target vessel revascularization, and bleeding events were analyzed after 1-year follow-up. At 1-year follow-up after stenting, major adverse cardiac events including death, myocardial infarction, and ischemic-driven TLR were lower in the triple group than the dual group. Major bleeding was similar in both the groups. In obese patients undergoing percutaneous coronary intervention, triple antiplatelet therapy was superior to dual antiplatelet therapy in decreasing thrombotic events in 12-month cardiac events, mainly driven by a decrease in the incidence of clopidogrel resistance.