The goal of this study was to evaluate the effect of extracorporeal membrane oxygenation (ECMO) on mortality in patients with cardiogenic shock excluding Impella and IABP use. The large Nationwide Inpatient Sample (NIS) database was utilized to study any association between the use of ECMO in adults over the age of 18 and mortality and complications with a diagnosis of cardiogenic shocks. ICD-10 codes for ECMO and cardiogenic shock for the available years 2016–2020 were utilized. A total of 796,585 (age 66.5 ± 14.4) patients had a diagnosis of cardiogenic shock excluding Impella. Of these patients, 13,160 (age 53.7 ± 15.4) were treated with ECMO without IABP use. Total inpatient mortality without any device was 32.7%. It was 47.9% with ECMO. In a multivariate analysis adjusting for 47 variables such as age, gender, race, lactic acidosis, three-vessel intervention, left main myocardial infarction, cardiomyopathy, systolic heart failure, acute ST-elevation myocardial infarction, peripheral vascular disease, chronic renal disease, etc., ECMO utilization remained highly associated with mortality (OR: 1.78, CI: 1.6–1.9, p < 0.001). Evaluating teaching hospitals only revealed similar findings. Major complications were also high in the ECMO cohort. In patients with cardiogenic shock, the use of ECMO was associated with the high in-hospital mortality regardless of comorbid condition, high-risk futures, or type of hospital.