Current evidence suggests that levosimendan may have a beneficial effect in the treatment of acute heart failure (AHF) or cardiogenic shock following primary percutaneous coronary intervention (PCI). However, there is a paucity of data on the use of levosimendan prior to PCI. Therefore, our pilot study aimed to assess the short-term prognosis of a new therapeutic protocol involving preprocedural infusion of levosimendan in patients with reduced left ventricular ejection fraction undergoing high-risk PCI for acute coronary syndrome (ACS). The study is a retrospective observational study, and the population includes all subjects who received levosimendan infusion prior to high-risk PCI for ACS. Subjects requiring urgent revascularization (cardiogenic shock, cardiac arrest) or with mechanical complications of ACS were excluded. The study cohort consisted of 90 subjects, predominantly men (91.1%) with significantly reduced left ventricular function (28.7% (12)) and advanced coronary artery disease, mean SYNTAX Score 25.8 (19.3-33). During in-hospital follow-up, we observed 2 primary outcomes-death. The major adverse cardiac and cerebrovascular events (MACCE) rate was 7.8%. Two clinical adverse events that did not lead to discontinuation were observed during the in-hospital period. Both were related to hypotension. In short-term observation, novel therapeutic approach in the management of high-risk PCI in ACS patients-pre-procedural levosimendan-was a relatively safe approach. No significant adverse events were reported.