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Introduction: Milrinone and dobutamine are inotropes commonly used in cardiogenic shock, yet limited literature exists to provide guidance on choosing an individual agent. Prompted by a dobutamine shortage at Ascension St. Vincent Indianapolis, this study’s purpose is to evaluate institutional utilization and compare outcomes in those who received either agent as initial inotropic support. Methods: This single-center, retrospective study evaluated adult patients admitted to the ICU or telemetry units in 2021, prior to the dobutamine shortage. Included patients received initial therapy with milrinone or dobutamine for ≥ 24 hours and met the Society for Cardiovascular Angiography and Interventions cardiogenic shock diagnostic criteria. Patients were randomized in a 3:1 dobutamine to milrinone ratio for analysis, based on institution-specific usage, with a goal of 100 total patients to be evaluated. Results: Among 100 patients, the dobutamine group had a lower rate of ventricular arrhythmia history (27.4% vs. 55.6%, p = 0.017) and lower baseline mean arterial pressures (63 vs. 69 mmHg, p = 0.017) compared to milrinone. The milrinone group had a longer median hospital LOS (38 vs. 13 days, p = 0.0019), ICU LOS (25 vs. 9 days, p = 0.015), and inotrope therapy duration (21.8 vs. 7.9 days; p = 0.00053). Milrinone had a higher rate of cardiac transplantation or mechanical support (74.1% vs. 34.2%, 95% CI 1.42-3.32; p < 0.0006), and nearly half of the milrinone group transitioned to dobutamine (48.1% vs. 2.7%, 95% CI 5.25-58.65; p < 0.00001). There was no significant difference in inpatient mortality (26% vs. 11.1%, p = 0.17), cardiac arrest (5.5% vs. 7.4%, p = 0.66), or renal replacement therapy (RRT) initiation (20.5% vs. 18.5%, p = 1). Conclusions: Choice of initial inotrope in cardiogenic shock was significantly influenced by the degree of hypotension and ventricular arrhythmia history. Patients requiring bridging with inotropes to advanced therapies were more likely to initially receive milrinone, contributing to the longer median inotrope therapy duration and LOS seen in the milrinone group overall. Similar to prior studies, no significant differences were seen in inpatient mortality, cardiac arrest, or RRT, though further research is needed given the rate of dobutamine use in both groups during admission.