Objective To compare the effects of levosimendan vs epinephrine on low cardiac output syndrome (LCOS) after cardiac surgery. Methods Forty-eight patients with LCOS after cardiac surgery in our department from 2011 to 2012 were enrolled in this prospective study. They were randomly assigned to levosimendan group [n＝23, 0.05 to 0.2μg·(kg·min) for 24h] and epinephrine group [n＝25, 0.01 to 0.04μg·(kg·min) for 1 week] to maintain the mean arterial pressure ≥65mmHg. Their heart rate, mean arterial pressure, pulmonary artery wedge pressure, central venous pressure, cardiac output, cardiac index, systemic vascular resistance and cardiac function (evaluated by echocardiography before and on 3 and 7d after drug injection, respectively) were monitored as well as blood lactate and kidney function (urea nitrogen, serum creatinine and urine output before and at 24 and 48h after drug injection, respectively). The postoperative complications and prognosis were also observed. Results Cardiac output and cardiac index were significantly increased, but blood lactate was obviously decreased after the drug injection compared with before the injection (P＜0.05). Levosimendan injection for 48h resulted in significant changes in urea nitrogen, serum creatinine and urine output (P＜0.05), with the first one significantly lower than that of epinephrine group (P＜0.05). There was significantly lower incidence of atrial fibrillation in levosimendan group than in epinephrine group (P＜0.05). Levosimendan injection also caused a decreasing trend of post-operative complications. Conclusion Both leosimendan and adrenaline obviously improve the hemodynamic indices and cardiac functions, and tissue perfusion in LCOS patients after cardiac surgery. Leosimendan is more beneficial to renal function.