Objective: To evaluate the clinical efficacy of levosimendan versus dobutamine in critically ill patients requiring inotropic support. Methods: Clinical trials were searched in PubMed, EMBASE, and the Cochrane Central Registry of Clinical Trials, as well as Web of Science. Studies were included if they compared levosimendan with dobutamine in critically ill patients requiring inotropic support, and provided at least one outcome of interest. Outcomes of interest included mortality, incidence of hypotension, supraventricular arrhythmias, and ventricular arrhythmias. Results: Data from a total of 3052 patients from 22 randomized controlled trials (RCTs) were included in the analysis. Overall analysis showed that the use of levosimendan was associated with a significant reduction in mortality (269 of 1373 [19.6%] in the levosimendan group, versus 328 of 1278 [25.7%] in the dobutamine group, risk ratio (RR)=0.81, 95% confidence interval (CI) 0.70-0.92, P for effect=0.002). Subgroup analysis indicated that the benefit from levosimendan could be found in the subpopulations of cardiac surgery, ischemic heart failure, and concomitant β-blocker therapy in comparison with dobutamine. There was no significant difference in the incidence of hypotension, supraventricular arrhythmias, or ventricular arrhythmias between the two drugs. Conclusions: In contrast with dobutamine, levosimendan is associated with a significant improvement in mortality in critically ill patients requiring inotropic support. Patients having cardiac surgery, with ischemic heart failure, and receiving concomitant β-blocker therapy may benefit from levosimendan. More RCTs are required to address the questions about no positive outcomes in the subpopulation in a cardiology setting, and to confirm the advantages in long-term prognosis. Objective: To evaluate the clinical efficacy of levosimendan versus dobutamine in critically ill patients requiring inotropic support. Methods: Clinical trials were searched in PubMed, EMBASE, and the Cochrane Central Registry of Clinical Trials, as well as Web of Science. Studies were included if they compared levosimendan with dobutamine in critically ill patients requiring inotropic support, and provided at least one outcome of interest. Outcomes of interest included mortality, incidence of hypotension, supraventricular arrhythmias, and ventricular arrhythmias. Results: Data from a total of 3052 patients from 22 Overallized analysis showed that the use of levosimendan was associated with a significant reduction in mortality (269 of 1373 [19.6%] in the levosimendan group, versus 328 of 1278 [25.7%] in the dobutamine group, risk ratio (RR) = 0.81, 95% confidence interval (CI) 0.70-0.92, Pfor effect = 0.002) indicated that the benefit from levosimendan could be found in the subpopulations of cardiac surgery, ischemic heart failure, and concomitant beta-blocker therapy in comparison with dobutamine. There was no significant difference in the incidence of hypotension, supraventricular arrhythmias, or ventricular arrhythmias between the Two drugs. Conclusions: In contrast with dobutamine, levosimendan is associated with a significant improvement in mortality in critically ill patients requiring inotropic support. Patients having cardiac surgery, with ischemic heart failure, and receiving concomitant beta-blocker therapy may benefit from levosimendan. More RCTs are required to address the questions about no positive outcomes in the subpopulation in a cardiology setting, and to confirm the advantages in long-term prognosis.