A pilot study indicates that delaying reperfusion in ST-segment elevation myocardial infarction to allow enough time for mechanical unloading of the left ventricle (LV) to precondition the myocardium and reduce injury is feasible within a short door-to-balloon time. Rates of major adverse cardiovascular and cerebrovascular events at 30 days in patients assigned to unloading of the LV with the Impella CP device (Abiomed) followed by immediate reperfusion (n = 25; door-to-balloon time 72 min) were similar to those in patients assigned to delayed reperfusion after 30 min of unloading (n = 25; door-to-balloon time 97 min) (8% versus 12%), and delaying reperfusion did not affect 30-day mean infarct size. No major safety signals were identified that would preclude a larger, pivotal trial.