Objective: To investigate effects of nicorandil combined with trimetazidine on endothelial cell microparticles (EMPs), endothelial cell-specific molecule-1 (ESM-1) and high-sensitivity C-reactive protein (hs-CRP) in patients with acute myocardial infarction after percutaneous coronary intervention (PCI). Methods: In total, 103 patients with acute myocardial infarction treated in our hospital were enrolled as participants of a retrospective analysis. In line with the therapeutic methods used they were divided into two groups where PCI was given. Later, patients in the control group were then managed with trimetazidine and patients in the observation group were managed with trimetazidine combined with nicorandil. In this context, the clinical efficacy, changes in EMPs, ESM-1, hs-CRP, cardiac parameters, and incidence of adverse cardiovascular events within 30 days of the treatment were recorded. Results: (1) The management used in the observation group generated superior total validity (94.23%) compared with that used in the control group (64.71%) (X-2 =13.828, P<0.05). (2) Levels of EMPs, ESM-1 and hs-CRP 7 days after treatment in patients in the observation group were greater than those in the control group (P<0.05). (3) LVEDVI and LVESVI 7 days after treatment of patients in the observation group became lower, while PER and LVEF were higher, than those of the patients in the control group (P<0.05). (4) The incidence of adverse cardiovascular events, within 30 days of treatment, in the observation group was 3.85% compared with 5.88% in the control group, with non-significant differences (X-2 =0.231, P>0.05). Conclusion: The application of nicorandil combined with trimetazidine is conductive to down-regulation of the expression of EMPs, ESM-1 and hs-CRP and ameliorate cardiac issues in patients with acute myocardial infarction after PCI. This treatment combination offers a good short-term prognosis which is promising.