BACKGROUND There is evidence that trimetazidine, an anti-ischaemic agent with a direct cytoprotective effect on the myocardium, is effective in stable angina. However, it is not clear whether trimetazidine can improve the mechanical efficiency of chronically dysfunctional myocardium, and whether this potentially beneficial effect can translate into improvements in left ventricular function as well as functional capacity. METHODS Thirty-eight patients (52.7 +/- 8 years) with post-necrotic left ventricular dysfunction (ejection fraction: 33 +/- 5%) and multivessel coronary artery disease were studied. Patients were randomized into two matched groups. Group A received trimetazidine (20 mg three times daily) for 2 months, while group B received a placebo during the same period. The usual antianginal medications were not altered during the study. At baseline and after 2 months, all patients underwent low-dose dobutamine echocardiography (5-20 microg x kg(-1) x min(-1)), and a symptom-limited cardiopulmonary exercise test. RESULTS On initial evaluation, systolic wall thickening score index, heart rate, systolic blood pressure and rate pressure product were similar at rest and peak dobutamine in both groups. However, at 2 months, group A patients had significant improvements in the rest and peak systolic wall thickening score index (13% and 20.7%, P<0.001) and ejection fraction (19.7% and 14.1%, P<0.001) without concomitant changes in heart rate and blood pressure. Peak VO2 was also significantly increased in patients taking trimetazidine (15%, P=0.001 vs controls). CONCLUSIONS In patients with ischaemic cardiomyopathy, trimetazidine improves the contractile response of chronically dysfunctional myocardium to dobutamine without haemodynamic changes. This effect was associated with improvements in left ventricular function and peak VO2.