Background: Patients undergoing cardiac surgery are becoming older and with greater comorbidities, carrying an increased risk for perioperative complications, which result in higher mortality and higher costs for the health care service. Objective: Our study is randomized, double-blind, placebo-controlled, multicenter clinical study to evaluate the efficacy of levosimendan given preoperatively in high-risk patients with Left ventricular ejection fraction (LVEF) ≤35% undergoing cardiac surgery on cardiopulmonary bypass (CPB). Patients and methods: This study was carried out in Cardiothoracic Department, Natinaol Heart Institute, Al Hussin hospital, Air Forced Specialized Hospital, and Saudi German Hospital. 60 patients treated with study drug were enrolled, the study population was drawn from patients with an LVEF ≤35% scheduled to undergo cardiac surgery with planned CPB. Results: Our results showed that the relative risk for postoperative mortality at 60 days was reduced by 10% in the levosimendan group when compared with the control group [4 of 30 (13%) in the levosimendan group vs 7 of 30 (23%) in the control group] with p value =0.5, however the incidence of 30-day out-of-hospital complications was not statistically different between the two groups. In the levosimendan group, no significant reduction in the rate of renal replacement therapy was observed [7 of 30 (23.3%) in the levosimendan group vs 8 of 30 (26.7%) in the control group]. Conclusion: Levosimendan is safe and well tolerated in patients undergoing cardiac surgery with cardiopulmonary bypass who have low LVEF and are at risk of the development of postoperative low cardiac output syndrome (LCOS).