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The optimal revascularization strategy for residual coronary stenosis following primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) remains controversial. This is a retrospective single-centre study including patients with STEMI and MVD. Based on the revascularization strategy, 3 groups were identified: (1) culprit only (CO), (2) ad hoc multivessel revascularization (MVR), and (3) staged MVR. Clinical outcomes were compared in terms of major adverse cardiac events (MACE), a composite of cardiac death, any myocardial infarction, and any unplanned revascularization at a long-term follow-up. A total of 958 patients were evaluated, 489 in the CO, 254 in the ad hoc, and 215 in the staged group. In the staged group, 65.6% of the patients received planned percutaneous coronary intervention, 9.7% coronary artery bypass grafting, 8.4% no further intervention after lesion reassessment, and in 16.3% an event occurred before the planned procedure. At 1,095 days, MACE was 36.1%, 16.7%, and 31% for CO, ad hoc, and staged groups, respectively. A MVR strategy was associated with lower rate of all-cause death compared with CO (HR 0.50; 95%CI [0.31 to 0.80]; p = 0.004). Complete revascularization reduced the rate of MACE (HR 0.30 [0.21 to 0.43] p < 0.001) compared with incomplete revascularization. Ad hoc MVR had lower rate of MACE compared with staged MVR (HR 0.61 [0.39 to 0.96] p = 0.032) mainly driven by less unplanned revascularizations. In conclusion, in patients with STEMI and MVD, complete revascularization reduced the risk of MACE. Ad hoc MVR appeared a reasonable strategy with lower contrast and stent usage and costs., (Copyright © 2020 Elsevier Inc. All rights reserved.)