Type 2 diabetes mellitus (T2DM) is a risk factor for the development of coronary artery disease (CAD). In patients with acute coronary syndrome (ACS), guidelines recommend a potent P2Y12 inhibitor in addition to aspirin. For those with complicated and advanced CAD requiring complex percutaneous coronary intervention (PCI), the risk for adverse ischemic events is even higher. Prolonged dual antiplatelet therapy (DAPT) use is controversial. A new antiplatelet regimen after PCI should be considered. In this analysis, we aimed to systematically show the impact of long-term ticagrelor monotherapy after a short course of DAPT use on the outcomes in patients with T2DM following PCI.Electronic databases were searched for relevant publications. Studies that were based on patients with T2DM and that included patients with T2DM were selected on the basis of the inclusion and exclusion criteria. Statistical analysis was carried out with RevMan software. The data are presented as risk ratios (RR) with 95% confidence intervals (CI).A total of 8621 patients were included in this analysis, whereby 4357 participants with T2DM were assigned to ticagrelor monotherapy and 4264 were assigned to DAPT. Our results showed long-term ticagrelor monotherapy after a short course of DAPT use to be associated with a significantly lower risk of major adverse cardiac events (RR 0.86, 95% CI 0.77-0.98; P = 0.02) and all-cause mortality (RR 0.77, 95% CI 0.60-0.98; P = 0.03). However, no significant difference was observed in cardiac death, myocardial infarction, stroke, stent thrombosis, or repeated revascularization. Ticagrelor monotherapy was associated with significantly lower risk of thrombolysis in myocardial infarction (TIMI) defined minor or major bleeding (RR 0.71, 95% CI 0.54-0.93; P = 0.01) compared with the DAPT regimen.Long-term ticagrelor monotherapy after a short course of DAPT use showed better results in patients with T2DM following PCI. Therefore, ticagrelor monotherapy after a short course of DAPT use could be considered an evolution in antiplatelet therapy of this decade for the treatment of patients with T2DM after PCI. However, newer studies with a larger population size and cost-effectiveness are factors that should further be considered.© 2022. The Author(s).