Objective To explore the incidence, causes and influencing factors of premature ticagrelor discontinuation (PTD) in patients with acute coronary syndrome (ACS). Methods A total of 400 hospitalized ACS patients who were treated with aspirin and ticagrelor in the Department of Cardiovasology, Changhai Hospital, Naval Medical University (Second Military Medical University) from Jan. to Oct. 2018 were retrospectively enrolled. Baseline data were collected and patients were followed up to analyze the incidence, causes and influencing factors of PTD in ACS patients. Results At 12 months after discharge, PTD occurred in 49 patients (12.2%), and was free in 351 patients (87.8%). The proportions of patients with age>75 years, heart failure history or previous percutaneous coronary intervention (PCI) and the levels of serum potassium and urea in PTD group were significantly higher than those in non-PTD group (P=0.004, 0.031, 0.028, 0.037, 0.001). The proportion of patients using β-blocker and the severity of vascular stenosis in PTD group were significantly lower than those in non-PTD group (P=0.041, 0.018). Dyspnea (22.4%, 11/49), drug unavailability (18.4%, 9/49) and bleeding (12.2%, 6/49) were the three most common causes of PTD. PTD occurred in all dyspnea patients with modified British Medical Research Council (mMRC) being grade 2 or higher (two cases with grade 1, six cases with grade 2, two cases with grade 3, and one case with grade 4). Kaplan-Meier curve analysis showed that 67.3% (33/49) of patients with PTD occurred within 90 days after discharge. Multivariate logistic regression analysis showed that age>75 years old (odds ratio [OR]=2.58, 95% confidence interval [CI] 1.26-5.26, P=0.009) and elevated urea (OR=1.17, 95% CI 1.04-1.30, P=0.007) were independent predictors of PTD in ACS patients, while severity of vascular stenosis (OR=0.95, 95% CI 0.92-0.98, P=0.001) was the related factor of adherence to ticagrelor. Conclusion The incidence of PTD in ACS patients during dual antiplatelet therapy is 12.2%. For dyspnea patients with mMRC score of grade 2 or higher, P₂Y₁₂ receptor antagonist should be replaced in time. Age> 75 years old is an independent predictor of PTD in ACS patients and more attention is needed for elderly patients taking ticagrelor whether they have dyspnea or PTD.