Objectives: This study sought to determine frequency, associated factors, and impact of bleeding in infarct-related cardiogenic shock. Background: Early revascularization is associated with improved survival in patients with acute myocardial infarction complicated by cardiogenic shock. On the downside, invasive treatment and accompanying antithrombotic therapies are associated with an increased bleeding risk. Prospective data assessing the incidence, severity, risk factors, and prognostic implication of bleeding in patients with cardiogenic shock are scarce. Methods: As a pre-defined subanalysis of the CULPRIT-SHOCK (PCI Strategies in Patients with Acute Myocardial Infarction and Cardiogenic Shock) randomized trial, we examined distribution of bleeding events in 684 patients with infarct-related cardiogenic shock and compared patients with any bleeding to those without. Results: A total of 21.5% patients experienced at least 1 bleeding event until 30 days after randomization. The vast majority of bleeding (57%) occurred within the first 2 days of hospitalization. Patients with bleeding had prolonged catecholamine treatment and mechanical ventilation and there was a significant association with sepsis, peripheral ischemic complications, new atrial fibrillation, and ventricular fibrillation. In multivariable analysis, bleeding was associated with a significantly higher mortality (hazard ratio: 2.11; 95% confidence interval: 1.63 to 2.75; p < 0.0001). Treatment with active mechanical support by extracorporeal membrane oxygenation or Impella emerged as the major risk factor for bleeding. Conclusions: Risk of bleeding in infarct-related cardiogenic shock is high and associated with increased mortality.