Aim To observe the changes of serum high sensitivity C-reactive protein (hs-CRP) and endothelial cell-specific molecule-1 (ESM-1) levels and short-term prognosis of ticagrelor in treatment of patients with acute ST-segment elevation myocardial infarction (STEMI). Methods A total of 107 patients with acute STEMI were selected, all of whom were treated in department of cardiology in our hospital for new onset of symptoms and received emergency PCI successfully. The patients were divided into two groups according to the application of ticagrelor in dual antiplatelet therapy (DAPT):ticagrelor group (n=54) and clopidogrel group (n=53). Two groups of patients were observed for changes of hs-CRP and ESM-1 immediately after admission as well as 24 h, 4 d and 7 d after medication, their correlation, and influences of ticagrelor on short-term prognosis of patients with acute STEMI. Results Hs-CRP and ESM-1 of the two groups of patients were obviously elevated at 24 h after medication, and there were statistical differences (P＜0.05), and hs-CRP and ESM-1 of the two groups of patients were decreasing at 4 d and 7 d, with statistically significant differences (P＜0.05); ESM-1 was increased with the increase of hs-CRP, showing a positive correlation between ESM-1 and hs-CRP (r=0.535, P＜0.001), there were no statistical differences in comparison between the two groups in incidences of ischemic end event, hemorrhagic event and total adverse events (P＞0.05). Conclusions Ticagrelor can more quickly reduce the cell inflammation and stabilize endothelium in treatment of STEMI patients, so as to improve the stability of atherosclerotic plaque, reduce the formation of thrombus and ischemic end events, but it does not increase the risk of bleeding, which is worth of clinical application.