Acute cardiac failure caused by myocardial infarction or inadequate cardioprotection during heart surgery is associated with increased mortality and morbidity. Levosimendan is a new drug used in heart failure though it is limited by the systemic hypotension, which develops with intravenous administration. Intracoronary (IC) administration however should affect systemic circulation less while maintaining the beneficial cardiac effects of the drug. We herewith report the results from the first such clinical series. Levosimendan was administered IC in 33 consecutive patients who developed cardiogenic shock during heart surgery and were unable to wean off cardiopulmonary bypass despite maximal support. Preadministration/postadministration coronary graft flows, hemodynamic parameters, left ventricular function, and metabolic requirements were measured and compared. Levosimendan significantly increased graft flows and improved hemodynamic parameters. Systolic blood pressure (93 ± 26.4 vs. 106 ± 18.2 mm Hg, P < 0.05) and cardiac index (2.0 ± 0.5 vs. 3.1 ± 0.2, P < 0.001) were increased, whereas systemic vascular resistance (1470.7 ± 114 vs. 1195.8 ± 112, P < 0.01) was reduced. Better myocardial perfusion improved metabolic requirements, with myocardial oxygen extraction and glucose uptake increasing by 72% and 74%, respectively, whereas lactate production was reduced by 64%. Echocardiography demonstrated additional ventricular segment recruitment. Therefore, IC Levosimendan administration in acute heart failure is safe and efficacious producing improved cardiac function without significant detrimental hypotension.