Key Points The Impella percutaneous microaxial ventricular assist device provides significant ventricular unloading, but at the cost of increased major bleeding, hemolysis, and thrombocytopenia. The present study shows that nearly all patients develop thrombocytopenia within 7 days of Impella insertion with 81% having a >50% decrease. Platelet recovery occurs following device removal. Recognition of Impella‐related thrombocytopenia can reduce the concern for heparin‐induced thrombocytopenia and avoid the potential risks of direct thrombin inhibitors.