•This study represents the largest reported experience of Impella-supported myocarditis cases to date.•Patients treated with Impella for myocarditis in routine clinical practice have severe LV dysfunction and are in cardiogenic shock refractory to conventional therapy with the use of vasopressors, inotropes, and intra-aortic balloon pump.•Impella use appears to be safe in the settings of myocarditis complicated with cardiogenic shock.•Impella use can provide effective circulatory and ventricular support to allow for hemodynamic and myocardial recovery in patients with myocarditis complicated with cardiogenic shock. Myocarditis complicated by cardiogenic shock remains a complex problem. The use of acute mechanical circulatory support devices for cardiogenic shock is growing. We explored the utility of Impella transvalvular microaxial flow catheters in the setting of myocarditis with cardiogenic shock. We retrospectively analyzed data from 21 sites within the cVAD registry, an ongoing multicenter voluntary registry at sites in North America and Europe that have used Impella in patients with myocarditis. Myocarditis was defined by endomyocardial biopsy (n = 11) or by clinical history without angiographic evidence of coronary disease (n = 23). A total of 34 patients received an Impella 2.5, CP, 5.0, or RP device for cardiogenic shock complicating myocarditis. Baseline characteristics included age 42 ± 17 years, left ventricular ejection fraction (LVEF) 18% ± 10%, cardiac index 1.82 ± 0.46 L·min−1·m−2, pulmonary capillary wedge pressure 25 ± 7 mm Hg, and lactate 27 ± 31 mg/dL. Before Impella placement, 32% (n = 11) of patients required intra-aortic balloon pump. Mean duration of Impella support was 91 ± 74 hours; 21 of 34 patients (62%) survived the index hospitalization and were discharged with an improved mean LVEF of 37.32% ± 20.31% (P = .001); 15 patients recovered with successful support, 5 patients were transferred to another hospital on initial Impella support, 1 patient underwent orthotopic heart transplantation. Ten patients required transition to another mechanical circulatory support device. This is the largest analysis of Impella-supported myocarditis cases to date. The use of Impella appears to be safe and effective in the settings of myocarditis complicated by cardiogenic shock.