Background Clinical outcomes of acute myocardial infarction complicated by cardiogenic shock remain poor with high in-hospital mortality. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been widely used for patients with acute myocardial infarction complicated by cardiogenic shock refractory to conservative therapy, which is likely fatal without mechanical circulatory support. However, whether additional intra-aortic balloon pumping (IABP) use during VA-ECMO support improves clinical outcomes remains controversial. This study sought to investigate prognostic impact of the combined VA-ECMO plus IABP treatment compared with VA-ECMO alone. Methods and Results From the nationwide Japanese administrative case-mix Diagnostic Procedure Combination (DPC), the JROAD (Japanese Registry of All Cardiac and Vascular Diseases)-DPC, we identified 3815 patients with acute myocardial infarction complicated by cardiogenic shock who underwent primary percutaneous coronary intervention and managed with VA-ECMO. Of these, 2964 patients (77.7%) were managed with IABP (VA-ECMO plus IABP), whereas 851 (22.3%) were managed without IABP (VA-ECMO alone). We compared in-hospital, 7-day, and 30-day mortality between the VA-ECMO plus IABP versus the VA-ECMO alone support. Patients managed with VA-ECMO plus IABP demonstrated significantly lower in-hospital, 7-day, and 30-day mortality than those managed with VA-ECMO alone (adjusted odds ratios [95% CI] of 0.47 [95% CI, 0.38-0.59], 0.41 [95% CI, 0.33-0.51], and 0.30 [95% CI, 0.25-0.37], respectively). The findings were consistent in the propensity matching and inverse probability of treatment-weighting models. Conclusions This large-scale, nationwide study demonstrated that the combination of VA-ECMO plus IABP support was associated with significantly lower mortality compared with VA-ECMO support alone in patients presenting with acute myocardial infarction complicated by cardiogenic shock who underwent primary percutaneous coronary intervention.