Heart transplantation is considered nowadays the gold standard in the therapy of chronic and terminal heart insufficiency. Primary organ failure after heart transplantation is a severe complication generally related to prolonged ischemia time, poor quality of the organ, or acute rejection. All these factors can potentially lead to multiorgan failure. Pharmacological and mechanical support for these patients is limited and often related to side effects. Ca2+ sensitizers have been proposed to increase cardiac contractility without altering intracellular Ca2+ levels, thus avoiding the side effects of Ca2+ overload. We report two cases of heart transplanted patients suffering from acute graft failure in the early postoperative period who recovered after intravenous administration of levosimendan, a Ca2+ sensitizer.