Background: The association of obesity on outcomes in patients with cardiogenic shock requiring acute mechanical circulatory support has not been thoroughly investigated. Methods: We evaluated the National Readmission Database for adults with either acute myocardial infarction or heart failure complicated by cardiogenic shock requiring acute mechanical circulatory support between January 2016 and November 2017. Exposure was assessed using International Classification of Diseases , Tenth Revision codes for the degree of obesity with the reference being body mass index (BMI) of 20.0 to 29.9 group. Multiple logistic regression and Cox regression analysis were used to analyze in-hospital mortality and 30-day readmission, respectively. Results: The survey-weighted sample included a total of 35 555 hospitalizations with a mean age of 65.4±0.2 years and 29.8% females. Obesity was associated with higher in-hospital mortality (no obesity, 26.4% [BMI, 20.0–29.9] versus class I obesity, 25.0% [BMI, 30.0–34.9] versus class II obesity, 28.7% [BMI, 35.0–39.9] versus class III obesity, 34.9% [BMI, ≥40]; P <0.001). On stratified analysis, compared with a nonobese phenotype, younger adults (age <60) with class II and class III obesity (odds ratio, 1.9 [95% CI, 1.1–3.5], P =0.02; odds ratio, 2.1 [95% CI, 1.2–3.7], P =0.01) and older adults (age ≥60) with class III obesity (odds ratio, 1.7 [95% CI, 1.2–2.4], P =0.005) had higher mortality. There was no association between the degree of obesity and 30-day readmission. Conclusions: Among adults with acute myocardial infarction or acute heart failure resulting in cardiogenic shock requiring acute mechanical circulatory support, younger adults with class II and class III obesity and older patients with class III obesity have a higher risk of in-hospital mortality compared with nonobese patients.