The optimal strategy for patients with an acute myocardial infarction (MI) and multivessel (MV) coronary artery disease complicated by cardiogenic shock (CS) remains unknown. We conducted a meta-analysis of all randomized controlled trials and observational studies that reported adjusted effect measures to evaluate the association of MV-PCI (percutaneous coronary intervention), compared with culprit only (C)-PCI, with cardiovascular events in patients admitted for CS and MV disease. We identified 12 studies (n = 1 randomized controlled trials, n = 11 observational) that included 7,417 patients (n = 1,809 treated with MV-PCI and n = 5,608 with C-PCI). When compared with C-PCI, MV-PCI was not associated with an increased risk of short-term death (odds ratio [OR] 1.14, 95% confidence interval [CI] 0.87 to 1.48, p = 0.35 and adjusted OR [OR_adj] 1.00, 95% CI 0.70 to 1.43, p = 1.00). In-hospital and/or short-term mortality tended to be higher with MV-PCI, when compared with C-PCI, for CS patients needing dialysis (ß 0.12, 95% CI from 0.049 to 0.198; p= 0.001), whereas MV-PCI was associated with lower in-hospital and/or short-term mortality in patients with an anterior MI (ß −0.022, 95% CI −0.03 to −0.01; p <0.001). MV-PCI strategy was associated with a more frequent need for dialysis or contrast-induced nephropathy after revascularization (OR 1.36, 95% CI 1.06 to 1.75, p = 0.02). In conclusion, MV-PCI seems not to increase risk of death during short- or long-term follow-up when compared with C-PCI in patients admitted for MV coronary artery disease and MI complicated by CS. Furthermore, it appears a more favorable strategy in patients with anterior MI, whereas the increased risk for AKI and its negative prognostic impact should be considered in decision-making process. Further studies are needed to confirm our hypothesis on in these subpopulations of CS patients.