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Background Despite the benefit of culprit‐only percutaneous coronary intervention (PCI) in the CULPRIT‐SHOCK (Culprit Lesion Only PCI Versus Multi‐vessel PCI in Cardiogenic Shock) trial, the optimal revascularization strategy for refractory cardiogenic shock (CS) requiring mechanical circulatory support devices remains controversial. This study aimed to compare clinical outcomes between the culprit‐only and immediate multivessel PCI strategies in patients with acute myocardial infarction complicated by CS who underwent venoarterial‐extracorporeal membrane oxygenation before revascularization. Methods and Results This study included patient‐pooled data from the RESCUE (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Devices for Korean Patients With Cardiogenic Shock) and SMC‐ECMO (Samsung Medical Center–Extracorporeal Membrane Oxygenation) registries. A total of 315 patients with acute myocardial infarction with multivessel disease who underwent venoarterial‐extracorporeal membrane oxygenation before revascularization attributable to refractory CS were included in this analysis. The study population was classified into culprit‐only versus immediate multivessel PCI according to nonculprit lesion treatment strategies. The primary end point was 30‐day mortality or renal‐replacement therapy, and the key secondary end point was 12‐month follow‐up mortality. Among the study population, 175 (55.6%) underwent culprit‐only PCI and 140 (44.4%) underwent immediate multivessel PCI. Compared with culprit‐only PCI, immediate multivessel PCI was associated with significantly lower risks of 30‐day mortality or renal‐replacement therapy (68.0% versus 54.3%; P =0.018) and all‐cause mortality during 12 months of follow‐up (59.5% versus 47.5%; hazard ratio [HR], 0.689 [95% CI, 0.506–0.939]; P =0.018) in patients with acute myocardial infarction and CS who underwent venoarterial‐extracorporeal membrane oxygenation before revascularization. These results were also consistent in the 99 pairs of propensity score–matched population (60.6% versus 43.6%; HR, 0.622 [95% CI, 0.420–0.922]; P =0.018). Conclusions Among patients with acute myocardial infarction with multivessel disease complicated by advanced CS requiring venoarterial‐extracorporeal membrane oxygenation before revascularization, immediate multivessel PCI was associated with lower incidences of 30‐day mortality or renal replacement therapy and 12‐month follow‐up mortality, compared with culprit‐only PCI. Registration Information clinicaltrials.gov . Identifier: NCT02985008.