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Introduction and Objectives: After ST-segment myocardial infarction (STEMI), the impact of different adverse events on prognosis remains unknown. We aimed to assess very long-term predictors of patient-oriented composite endpoints (POCE) and investigate whether the occurrence of target vessel failure (TVF) vs a non-TVF event as the first event could potentially influence subsequent outcomes., Methods: The EXAMINATION-EXTEND trial randomized STEMI patients to receive either an everolimus-eluting stent or a bare-metal stent. The follow-up period was 10 years. Predictors of POCE (a composite of all-cause death, any myocardial infarction, or any revascularization) were evaluated in the overall study population. The patients were stratified based on the type of first event (TVF-first vs non-TVF-first) and were compared in terms of subsequent POCE. TVF was defined as a composite of cardiac death, TV myocardial infarction, or TV revascularization., Results: Out of the 1498 enrolled patients, 529 (35.3%) experienced a POCE during the 10-year follow-up. Independent predictors of POCE were age, diabetes mellitus, previous myocardial infarction, peripheral arterial disease, and multivessel coronary disease. The first event was a TVF in 296 patients and was a non-TVF in 233 patients. No significant differences were observed between TVF-first and non-TVF-first patients in terms of subsequent POCE (21.7% vs 39.3%, time ratio 1.79; 95%CI, 0.87-3.67;P=.12) or its individual components., Conclusions: At the 10-year follow-up, approximately one-third of STEMI patients had experienced at least 1 POCE. Independent predictors of these events were age, diabetes, and more extensive atherosclerotic disease. The occurrence of a TVF or a non-TVF as the first event did not seem to influence subsequent outcomes., Trial Registration Number: NCT04462315., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)