Background: Despite high patency rates, primary angioplasty for myocardial infarction does not necessarily result in optimal myocardial reperfusion and limitation of infarct size. Experimentally, trimetazidine limits infarct size, decreases platelet aggregation, and reduces leukocyte influx into the infarct zone. To assess trimetazidine as adjunctive therapy to primary angioplasty for acute myocardial infarction a prospective, double-blind, placebo-controlled pilot trial was performed. Methods: 94 patients with acute myocardial infarction were randomized to receive trimetazidine (40 mg bolus followed by 60 mg/day intravenously for 48 h) ( n=44) or placebo ( n=50), starting before recanalization of the infarct vessel by primary angioplasty. Patients underwent continuous ST-segment monitoring to assess return of ST-segment deviation to baseline and presence of ST-segment exacerbation at the time of vessel recanalization. Infarct size was measured enzymatically from serial myoglobin measurements. Left ventricular angiography was performed before treatment and repeated at day 14. Results: Blinded ST segment analysis showed that despite higher initial ST deviation from baseline in the trimetazidine group (355 (32) vs. 278 (29) μV, P=0.07), there was an earlier and more marked return towards baseline within the first 6 h than in the placebo group ( P=0.014) (change: 245 (30) vs. 156 (31) μV respectively, P=0.044). There was a trend towards less frequent exacerbation of ST deviation at the time of recanalization in the trimetazidine group (23.3 vs. 42.2%, P=0.11). There was no difference in left ventricular wall motion at day 14, or in enzymatic infarct size. There was no side effect from treatment. Clinical outcomes were similar between groups. Conclusion: Trimetazidine was safe and led to earlier resolution of ST-segment elevation in patients treated by primary angioplasty for acute myocardial infarction.