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Limitations have been observed with the use of clopidogrel following percutaneous coronary intervention (PCI) indicating the urgent need of a more potent anti-platelet agent. We aimed to compare the efficacy and safety of ticagrelor versus clopidogrel following PCI.Online databases were searched for relevant studies (published between the years 2007 and 2017) comparing ticagrelor versus clopidogrel following coronary stenting. Primary outcomes assessed efficacy whereas secondary outcomes assessed safety. Odds ratios (OR) with 95% confidence intervals (CIs) based on a random effect model were calculated and the analysis was carried out by the RevMan 5.3 software.A total number of 25,632 patients with acute coronary syndrome (ACS) [12,992 patients with ST segment elevation myocardial infarction (STEMI) and 14,215 patients with non-ST segment elevation myocardial infarction (NSTEMI)] were included in this analysis, of whom 23,714 patients were revascularized by PCI. Results of this analysis did not show any significant difference in all-cause mortality, major adverse cardiac events (MACEs), myocardial infarction, stroke and stent thrombosis observed between ticagrelor and clopidogrel with (OR: 0.83, 95% CI: 0.67–1.03; P = .09), (OR: 0.64, 95% CI: 0.41–1.01; P = .06), (OR: 0.77, 95% CI: 0.57–1.03; P = .08), (OR: 0.85, 95% CI: 0.57–1.26; P = .42) and (OR: 0.70, 95% CI: 0.47–1.05; P =.09).However, ticagrelor was associated with a significantly higher minor and major bleeding with (OR: 1.57, 95% CI: 1.30–1.89; P = .00001) and (OR: 1.52, 95% CI: 1.01–2.29; P = 0.04) respectively. Dyspnea was also significantly higher in the ticagrelor group (OR: 2.64, 95% CI: 1.87–3.72; P = .00001).Ticagrelor and clopidogrel were comparable in terms of efficacy in these patients with ACS. However, the safety outcomes of ticagrelor should further be investigated.