The paucity of data to guide selection of specific vasoactive agents in patients with cardiogenic shock (CS) may lead to variability in practice patterns. The level of variability and specific factors that are associated with the use of vasoactive medications and inodilators have not been previously described. The CCCTN (Critical Care Cardiology Trials Network) is an international, multicenter network of cardiac intensive care units (CICUs) coordinated by the TIMI Study Group. This analysis included CICU admissions for CS from 2019 to 2023. Variation in the use of inodilator treatment (dobutamine/milrinone) was assessed with multivariable mixed-effects logistic modeling. A total of 3282 admissions from 37 CICUs comprised the analysis cohort. The use of vasoactive medications, including inodilator treatment, varied substantially across institutions. Patient-level variables associated with greater use of inodilators included history of heart failure (odds ratio, 1.98 [95% CI, 1.61-2.44]), biventricular failure (1.59 [95% CI, 1.27-2.00]), Society of Cardiovascular Angiography and Interventions stage D (1.34 [95% CI, 1.07-1.68]), valvular disease (1.34 [95% CI, 1.03-1.74]), and male sex (1.23 [95% CI, 1.02-1.49]). Variables associated with less inodilator use included cardiac arrest (0.33 [95% CI, 0.27-0.42]), right ventricular failure (0.50 [95% CI, 0.33-0.73]), Society of Cardiovascular Angiography and Interventions stage E (0.57 [95% CI, 0.41-0.81]), acute myocardial infarction-CS (0.71 [95% CI, 0.56-0.90]), peripheral arterial disease (0.73 [95% CI, 0.54-0.99]), older age (0.77 [95% CI, 0.72-0.83], per 10-year increase), and estimated glomerular filtration rate (0.96 [95% CI, 0.93-0.99], per 10 mL/min per 1.73 m2 increase). No individual measurable institution-level factors (eg, transplant center) were associated with variability in inodilator use. In mixed-effects logistic modeling, 45.7% of variation in inodilator use was attributed to patient-level factors and 22.7% to the random effect of individual CICU centers. Similarly, 35.3% of variation in the use of dobutamine versus milrinone was attributed to patient-level factors and 32.6% to the random effect of individual CICU centers. There is significant variation in vasoactive treatment and inodilator use in CS. Variation in inodilator use was associated with patient-level factors and with substantial individual CICU practice variation. Such variability underscores the need for additional high-quality evidence to guide vasoactive treatment strategies in CS.