Objective To investigate the impact of diabetes mellitus (DM) and stroke on long-term outcomes in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Methods Total 411 consecutive ACS patients undergoing PCI at the Ninth People′s Hospital of Zhengzhou between December 2014 and June 2018 were recruited, including 319 males and 92 females with a mean age of (64.7±10.1) years. These patients were divided into 4 groups according to the presence or absence of history of diabetes or stroke: non-DM non-stroke group (n=192) , DM group (n=140), stroke group (n=41), and DM+stroke group (n=38). The data of baseline demographic characteristics, clinical feature, coronary angiographic findings, and cardiovascular adverse events during long-term follow-up were obtained. Kaplan-Meier curves were used to investigate the long-term clinical outcomes among groups. Results The mean interval of follow-up was (24.1±13.8) months. Patients with DM+stroke had the highest rates of non-fetal myocardial infarction (χ2=24.932) , non-fetal stroke (χ2=9.434) , hospitalization due to heart failure/angina (χ2=69.290) , revascularization (χ2=22.918) , cardiovascular death(χ2=13.473)and all-cause death(χ2=17.724)as well as hard endpoint events (the sum of non-fetal myocardial infarction, non-fetal stroke, and all-cause death) (χ2=30.268)and combined major adverse cardiovascular events (MACE) (the sum of hard endpoint events, hospitalization due to heart failure/angina, and revascularization) (χ2=119.556)among 4 groups(all P 0.05) . Meanwhile, patients with DM+stroke presented significantly lower cumulated ratio free from combined MACE than patients with non-DM non-stroke (HR=5.423, 95%CI:2.941-10.036, P<0.01), and the cumulated ratio free from combined MACE also decreased significantly in DM+stroke group as compared to DM group or stroke group respectively (HR=1.859,95%CI: 1.167-2.962; HR=1.991,95%CI: 1.178-3.364; all P<0.01) . Conclusions ACS patients with combined history of DM and stroke have a worse long-term outcomes after PCI than those with DM alone or stroke alone or without DM or stroke. DM and stroke seemed to have an additive effect on decrease in the cumulative ratio free from combined MACE in ACS patients following PCI. Key words: Diabetes mellitus; Stroke; Acute coronary syndrome; Major adverse cardiovascular events; Percutaneous coronary intervention