BACKGROUND AND OBJECTIVE: Trimetazidine has mainly been used in coronary insufficiency, angina and elderly myocardial infarction. However, the effect of trimetazidine on the efficacy, heart rate variability (HRV) and protection of myocardial ischemia in elderly patients with acute coronary syndrome (ACS) remains unclear. This study aimed to investigate the effect of trimetazidine on the efficacy HRV and protection of myocardial ischemia in patients with ACS. METHODS: One hundred twenty two elderly ACS patients who were above 70 years were chosen and randomly divided into two groups. One group was given conventional therapy, such as aspirin, isosorbide mononitrate and fluvastatin, and the other group was administered trimetazidine in addition to conventional therapy. The treatment period was eight weeks. A PI-2.22B three-channel AECG system was used on every patient for 24 hour dynamic electrocardiogram monitoring and HRV analyses on the first day after admission and eight weeks after treatment. HRV, 24 hour RR intermediate stage standard deviation (SDNN), five minutes average normal cardiac cycle standard deviation in 24 hour (SDANN), 24 hour close together normal cardiac cycle difference value mean square root (rMSSD), the percentage of difference of close together RR intermediate > 50 ms account total RR intermediate (PNN50), high frequency (HF) and low frequency (LF) parameters of patients were observed before and after treatment. RESULTS: The SDNN, SDANN, rMSSD, PNN50 and HF parameters significantly increased compared with the conventional treatment group (all P < 0.05). LF and LF/HF were significantly decreased in the trimetazidine treatment group compared with those in the conventional treatment group (all P < 0.05). CONCLUSION: Trimetazidine improves HRV of elderly ACS patients and reduces cardiovascular events.