Objective: This study was conducted to evaluate long-term cardiovascular safety of gemigliptin in patients with type 2 diabetes mellitus (T2DM). Methods: This study was a multicenter, single-arm, prospective cohort study. After screening, the eligible patients over the age of 19 years with T2DM were enrolled, received gemigliptin, and were followed up for a median of 2.50 years (maximum of 4.35 years). The primary outcome was a composite of confirmed cardiovascular death, nonfatal myocardial infarction, or nonfatal ischemic stroke (major adverse cardiovascular event [MACE]). The key secondary outcomes were incidence of all-cause mortality and any other cardiovascular events (heart failure, hospitalization due to revascularization, peripheral vascular disease and unstable angina pectoris), and changes in HbA1c from baseline. Results: In total, 5,179 patients were enrolled and 5,113 were treated with gemigliptin. Overall, the primary outcome occurred in 26 patients for 12 months (estimated incidence by Cox proportional hazard model 0.49%, 95% confidence interval [CI]: 0.29-0.69%) and 54 patients for 54 months (estimated incidence by Cox proportional hazard model 1.35%, 95% CI: 0.92-1.77%). During the study period, the incidence of the each component of the primary composite outcome was 0.04% (0.2 events per 1000 person-years) for cardiovascular death, 0.51% (2.2 events per 1000 person-years) for nonfatal myocardial infarction, and 0.61% (2.5 events per 1000 person-years) for nonfatal ischemic stroke. The incidence of all-cause mortality was 0.82% (3.2 events per 1000 person-years), the incidence of heart failure, peripheral vascular disease, and unstable angina pectoris were all less than 0.3%, and hospitalization due to revascularization did not occur. The mean changes in HbA1c at 6 and 24 months from baseline were -0.94% and -0.83%, respectively. Conclusion: Gemigliptin showed a low incidence of the primary composite MACE and all-cause mortality in patient with T2DM. Thus, gemigliptin is expected to be used safely without increasing cardiovascular risk.