De-escalation from ticagrelor to clopidogrel in acute coronary syndrome (ACS) may occur for a variety of reasons, including side effects (bleeding and non-bleeding) and costs. This study sought to assess the prevalence of de-escalation from ticagrelor to clopidogrel and the occurrence of adverse clinical outcomes following de-escalation. We conducted a systematic review of clinical trials and real-world studies in ACS patients treated with ticagrelor. Real-world data on the prevalence of de-escalation during hospitalization or at discharge, after hospital discharge, and during the whole study period were included for meta-analysis. Major adverse cardiovascular events (MACE) and bleeding events occurring after de-escalation were also assessed. A total of 12 studies were eligible for meta-analysis of the prevalence of de-escalation. De-escalation from ticagrelor to clopidogrel therapy occurred with a mean prevalence of 19.8% [95% confidence interval (CI) 11.2-28.4%]. De-escalation occurred more frequently in-hospital or at discharge than after hospital discharge (23.7% vs. 15.8%). For assessment of clinical outcomes, a total of six studies were eligible for meta-analysis. Mean rate of MACE for patients with de-escalation was 2.1% (95% CI 1.1-4.1%) and the rate of major bleeding events was 1.3% (95% CI 0.4-4.5%). In conclusion, de-escalation commonly occurs in real-world practice. Although rates of major cardiovascular and bleeding events in this analysis were generally low, the profile of patients suitable for de-escalation, the impact of de-escalation on adverse clinical outcomes and how this is affected by the timing after index ACS warrants further large-scale investigation.