BACKGROUND Trimetazidine is a fatty oxidation inhibitor, leading to shifting of energy substrate from fatty acid oxidation toward glucose oxidation that leads to the reduction of oxygen requirement. The aims of the present study were to elucidate the effects of trimetazidine on psychomotor performance and vigilance on normal healthy volunteers. METHODS A total of 234 subjects (age 22-25 years) were recruited in this study. The volunteers were randomizing into two groups with 117 volunteers in each group. Group I received an inert starch capsule served as a control, and Group II received trimetazidine tablet 15 mg/day. The duration of therapy was 5 days. Test procedure was done at 9.00 a.m. on the psychomotor tester. Before the drug administration, prescore values were recorded and then after 5 days of therapy, the postscore values were recorded. RESULTS The placebo did not demonstrate a significant effect on all psychomotor performances and flicker-fusion elements (P > 0.05). Trimetazidine therapy produced a highly significant effect on all components of psychomotor performances and flicker-fusion parameters (P < 0.001) compared with pretreatment era. CONCLUSIONS We conclude that trimetazidine improves psychomotor performance and vigilance in normal healthy volunteers through advancing total reaction time and critical flicker-fusion frequency.