Severe postoperative complications can affect cardiac surgery patients. Levosimendan is a novel calcium sensitizer commonly administered after cardiac surgery. However, the patient benefits are controversial. PubMed, Embase, and the Cochrane library were systematically searched for randomized controlled trials comparing levosimendan with control in adult cardiac surgery patients. Twenty-five studies (3247 patients) were included. Pooled data indicated that levosimendan reduced mortality after cardiac surgery [odds ratio (OR) 0.63, 95% confidence interval (CI): 0.47–0.84, P = 0.001]. However, this reduction was restricted to patients with low (<50%) left ventricular ejection fraction (OR 0.49, 95% CI: 0.35–0.70, P = 0.0001). It significantly reduced the incidence of postoperative acute kidney injury (OR 0.55, 95% CI: 0.41–0.74, P < 0.0001) and renal replacement therapy use (OR 0.56, 95% CI: 0.39–0.80, P = 0.002). Moreover, levosimendan significantly shortened the duration of the intensive care unit stay (weighted mean differences −0.49 day, 95% CI: −0.75 to −0.24, P = 0.0002) and mechanical ventilation use (weighted mean differences −2.30 hours, 95% CI: −3.76 to −0.84, P = 0.002). In conclusion, levosimendan reduced the mortality in patients with low left ventricular ejection fraction and decreased the incidence of acute renal injury and renal replacement therapy use. In addition, it shortened the duration of the intensive care unit stay and mechanical ventilation use.