There is limited data on regional differences in patient characteristics, practice patterns, and clinical outcomes in patients with ST elevation myocardial infarction (STEMI) with cardiogenic shock (CS) in the United States (US). We aimed to identify variations in treatment methods and clinical outcomes in patients with STEMI CS between the 4 US regions. Using the National Inpatient Sample database, we identified adult patients admitted with STEMI associated with CS between 2006 and 2015 using ICD-9-DM codes. Based on the US regions (Northeast, Midwest, South, and West), we divided patients in 4 cohorts and compared baseline patient characteristics, clinical outcomes and procedural outcomes. A total of 186,316 patients with STEMI CS were included; 32,303 (17.3%) were hospitalized in the Northeast, 43,634 (23.4%) in the Midwest, 70,036 (37.8%) in the South, and 40,043 (21.5%) in the West. Although nonstatistically significant, the in-hospital mortality was higher in Northeast region (37.7%), followed by the South (36.6%), West (35.7%), and Midwest (35.2%). Rates of percutaneous coronary intervention were higher in the Midwest (68.5%) and lower in the Northeast (56%). The use of percutaneous ventricular assist device and ECMO was higher in the Northeast (3.3% and 2.2%) and lower in the West (2.1% and 0.4%). The median length of stay was similar among all 4 cohorts (6 days) but median hospital costs were higher in the West ($36, 614) and lower in the South ($28,795). In conclusion, there are significant geographic variations in practice patterns, healthcare cost, and in-hospital outcomes in patients with STEMI complicated by CS between 4 US regions.