Objective To investigate the clinical outcomes of de-escalation from ticagrelor to clopidogrel in patients with acute coronary syndrome (ACS) or those after undergoing percutaneous coronary intervention (PCI) in the real world. Methods A total of 746 consecutive inpatients with ACS or after PCI who received combined ticagrelor and aspirin therapy in the Department of Cardiology of Chinese PLA General Hospital from October 2013 to August 2016 and then de-escalated from ticagrelor to clopidogrel during hospitalization or within 1 year after discharge were recruited in this study. According to the de-escalation time, the patients were divided into acute phase group (≤1 month, n=212) and non-acute phase group (1-3 months, n=262; 3-6 months, n=156; 6－12 months, n=116). All patients were followed up for 1 year to analyze the causes of de-escalation. The incidences of primary endpoints [net clinical adverse events within 1 year:a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, target vessel reconstruction and bleeding type 2,3 or 5 according to the Bleeding Academic Research Consortium (BARC) criteria] and secondary endpoints (cardiovascular ischemic events and BARC type 2,3 or 5 bleeding events) were compared between the groups. SPSS statistics 26.0 was used for data analysis. Multivariate logistic regression analysis was employed to evaluate the risk of primary endpoints and secondary endpoints after the de-escalation at different time periods. Results The main reason for de-escalation was no serious stenosis on coronary angiogram in the acute phase group (23.1%), and was ticagrelor unavailable in the non-acute phase group (41.9%). The incidence rate of 1-year net clinical adverse events was slightly higher in the acute phase group than the non-acute 1-3 months group (14.6% vs 12.2%, HR=0.72,95%CI 0.41-1.26; P=0.252), but there was no statistical difference. The incidence rate in the non-acute 1-3 months group was significantly lower than that of the 3-6 months group (12.2% vs 19.2%; HR=1.90,95%CI 1.07-3.37; P=0.029) and that of the 6-12 months group (12.2% vs 21.6%; HR=1.48,95%CI 1.10－2.00; P=0.010). There was no significant difference in the incidence of 1-year cardiovascular ischemic events among the groups (P≥0.05). The rate of 1-year bleeding events was significantly lower in the non-acute 1-3 months group than the 6-12 months group (9.2% vs 15.5%; HR=1.42,95%CI 1.01-2.00; P=0.044). Conclusion In the real world, the patients with ACS or after PCI can obtain best net clinical benefit from de-escalation of ticagrelor to clopidogrel in an early non-acute phase (1-3 months).