Objective To explore whether trimetazidine could improve symptoms, cardiac functions and clinical outcomes in patients with heart failure (HF). Methods A systematic literature search was conducted to identify randomised controlled trials (RCT) of trimetazidine for HF between 1966 and May 2010 in Pubmed, the Cochrane Central Registry of Clinical Trials and EMBASE. Reports of trials were sought that compared trimetazidine with placebo control for chronic HF in adults, with outcomes including all-cause mortality, hospitalisation, cardiovascular events, changes in cardiac function parameters and exercise capacity. Results 17 trials with data for 955 patients were identified by the literature search. Trimetazidine therapy was associated with a significant improvement in left ventricular ejection fraction in patients with both ischaemic (weighted mean difference (WMD) with placebo 7.37%; 95% CI 6.05 to 8.70; p<0.01) and non-ischaemic HF (WMD 8.72%; 95% CI 5.51 to 11.92; p<0.01). With trimetazidine therapy, left ventricular end-systolic volume was significantly reduced (WMD 10.37 ml; 95% CI 15.46 to 5.29; p<0.01) and New York Heart Association classification was improved (WMD 0.41; 95% CI 0.51 to 0.31; p<0.01) as was exercise duration (WMD, 30.26 s; 95% CI 8.77 to 51.75; p<0.01). More importantly, trimetazidine had a significant protective effect for all-cause mortality (RR 0.29; 95% CI 0.17 to 0.49; p<0.00001) and cardiovascular events and hospitalisation (RR 0.42; 95% CI 0.30 to 0.58; p<0.00001). Conclusion Trimetazidine might be an effective strategy for treating HF. More studies, especially larger multicentre RCT, are warranted to clarify the effect of trimetazidine on HF.With more than 5 million prevalent cases and nearly 1 million hospital discharges yearly, heart failure (HF) represents a rapidly growing therapeutic challenge for healthcare providers.