OBJECTIVES: The aim of this study was to assess the impact of age on the safety and efficacy of ticagrelor monotherapy after percutaneous coronary intervention (PCI). BACKGROUND: As the risk for bleeding and ischemic complications after PCI increases with age, the authors conducted a pre-specified analysis of the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial to evaluate the possible benefits of ticagrelor monotherapy according to age. METHODS: The TWILIGHT trial enrolled patients undergoing PCI with drug-eluting stents who fulfilled at least 1 clinical and 1 angiographic high-risk criterion. Age ≥65 years was a clinical entry criterion. After 3 months of dual-antiplatelet therapy with ticagrelor, event-free patients were randomized to ticagrelor plus placebo or ticagrelor plus aspirin for an additional 12 months. The primary endpoint was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding. The key secondary endpoint was the composite of all-cause death, myocardial infarction, or stroke. RESULTS: A total of 3,113 patients (47.7%) were ≥65 years of age. At 1 year after randomization, ticagrelor monotherapy significantly reduced BARC type 2, 3, or 5 bleeding (4.5% vs. 8.2%; hazard ratio: 0.53; 95% confidence interval: 0.40 to 0.71) without increasing ischemic events (4.2% vs. 4.4%; hazard ratio: 0.96; 95% confidence interval: 0.68 to 1.35) compared with ticagrelor plus aspirin among patients ≥65 years of age. These findings were consistent in patients <65 years of age with respect to the primary (pinteraction = 0.62) and key secondary (pinteraction = 0.77) endpoints and across different age categories. CONCLUSIONS: A strategy of ticagrelor monotherapy following 3 months of dual-antiplatelet therapy significantly reduced clinically relevant bleeding compared with ticagrelor plus aspirin without an increase in ischemic events, irrespective of age.