Abstract: OBJECTIVE To systematically evaluate the efficacy and safety of selective novel cardiac myosin activators Omecamtiv mecarbil(OM) in the treatment of heart failure(HF). METHODS PubMed, EMbase, The Cochrane Library, Web of Science, CNKI, Science Direct, Wanfang Data and CBM databases were electronically searched to collect randomized controlled trials(RCT) about the efficacy and safety of selective cardiac myosin activators in the treatment of HF from inception to July 2021. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software. RESULTS A total of 6 RCT including 9 429 HF patients(4 763 in the experimental group, and 4 666 in the control group) were included. The results of meta-analysis showed that compared with control group, selective cardiac myosin activators did not reduce primary endpoints of HF patientsa composite of cardiovascular(CV) mortality and HF hospitalization(HHF) RR=1.19, 95% CI (0.67, 2.12), P=0.54, HHF rateRR=0.96, 95%CI(0.90, 1.03), P=0.29, CV mortalityRR=1.01, 95%CI(0.92, 1.10), P=0.88 and all-cause mortalityRR=1.00, 95%CI(0.93, 1.07), P=0.90. However, cardiac myosin activator OM significantly improved the Kansas City Cardiomyopathy Questionnaire(KCCQ) clinical scoresMD=2.50, 95% CI(2.47, 2.53), P<0.000 01, left ventricular ejection fraction (LVEF%)MD=7.20, 95%CI(2.51, 11.89), P=0.003, left ventricular end diastolic volume(LVEDV)MD=-0.35, 95% CI (-0.61, -0.08), P=0.009, left ventricular end systolic volume(LVESV)MD=-2.78, 95% CI(-3.70, -1.87), P<0.000 01 and stroke volume(SV)MD=8.80, 95% CI(1.37, 16.23), P=0.02 and other cardiac function parameters. Besides, the incidence of serious adverse events(SAE) was similar in two groupsRR=0.97, 95% CI(0.94, 1.01), P=0.16, and there were no significant differences between two groups in the incidence of acute kidney injury, symptomatic hypotension and dyspnea. CONCLUSION Current evidence indicates that selective cardiac myosin activators OM can significantly improve heart function parameters of KCCQ clinical scores, LVEF%, LVEDV, LVESV and stroke volume, without increasing the risk of adverse events, but have no significant benefit in terms of the composite of CV mortality and HHF, HHF rate, CV mortality and all-cause mortality in HF patients.