(1) Background: Mechanical circulatory support (MCS) in myocardial infarction associated cardiogenic shock is subject to debate. This analysis aims to elucidate the impact of MCS timing on patient outcomes, based on data from the PREPARE CS registry.; (2) Methods: PREPARE CS prospective registry included consecutive patients experiencing cardiogenic shock (SCAI Classes C-E) and were referred for cardiac catheterization. Present analysis included a subset, in whom MCS was used and underwent coronary intervention due to myocardial infarction. Patients were categorized into Upfront group versus Procedural group, depending on the timing of MCS introduction in relation to PCI. Endpoint was the in-hospital mortality; (3) Results: In total 71 patients were included. MCS was started prior to PCI in 33 (46%) patients (Upfront), whereas 38 (54%) received MCS during or after PCI initiation (Procedural). Baseline characteristics and hemodynamic parameters were comparable. The Upfront group had a higher utilization of Impella® device compared to extracorporeal membrane oxygenation (67% vs 33%), while the Procedural group exhibited a balanced use (50% vs 50%). Most patients suffered of multi-vessel disease in both groups (82% vs 84%, respectively; p=0.99) and most patients required complex PCI procedure, the latter was more prevalent in the Upfront group (94% vs 71%, respectively; p=0.02). Rates of complete revascularization were comparable (52% vs 34%, respectively; p=0.16). Procedural CPR was significantly more frequent in the Procedural group (45% vs 79%, p<0.05), still in-hospital mortality was similar (61% vs 79%, respectively; p=0.12); (4) Conclusions: Upfront implantation of MCS in myocardial infarction associated CS did not provide in-hospital survival benefit.