The aim of this work was to investigate the correlation between methylation of F2RL3 gene and coronary heart disease (CHD) with or without hypertension, secondary cardiovascular events and mortality. Sixty patients with CHD who underwent a cardiovascular rehabilitation program were recruited. Group A included 30 patients with hypertension and CHD, and group B included 30 patients with non-hypertensive CHD, followed-up for more than 8 years. F2RL3 gene methylation was characterized by Sequenom matrix assisted laser desorption ionization time flight mass spectrometry. The correlation between methylation of the F2RL3 gene, hypertension and secondary cardiovascular events and all-cause mortality was analyzed by multivariate Cox, regression models that estimated confounders to control risk ratios. The results showed that during the follow-up, 3 patients in Group A developed non-fatal stroke, 2 patients died of cardiovascular disease, 1 patient died of other causes, and 4 patients in Group B developed non-fatal myocardial infarction. After adjusting for known prognostic factors, Cox model analysis showed that methylation of F2RL3 gene was closely related to hypertension and mortality. After F2RL3 included in the regression model, the correlation between hypertension and all prognostic outcomes increased. In conclusion, the methylation of F2RL3 can affect the prognosis of different types of acute coronary syndrome and is closely related to mortality.