Objective: Vildagliptin has shown improvement in glycemic control across a wide disease spectrum in patients with type 2 diabetes mellitus (T2DM) with a low risk of hypoglycemia. The aim of this study is to evaluate the clinical effectiveness of vildagliptin plus metformin in patients with T2DM in real-life setting. Methods: This observational study retrieved data from the vildagliptin post-market surveillance (PMS), vildagliptin/metformin PMS, and a retrospective observational study of vildagliptin/metformin. The effectiveness endpoint was the proportion of patients achieving glycemic target (HbA1c ≤ 7.0%) at 24 weeks. Results: Total 4,303 subjects were recruited. Of these subjects, 2,087 subjects were eligible for analysis. Mean age of patients and duration of T2DM were 56.99 ± 11.25, 6.24 ± 5.77 years, respectively. Overall, 58.94% patients achieved an HbA1c target of ≤ 7.0% at 24 weeks. Higher glycemic target achievement rate were showed in subjects who belonged to baseline HbA1c < 7.5% group (84.64% vs HbA1c ≥ 7.5%, 43.97%), hospital group (67.95% vs clinic 52.33%) and vildagliptin/metformin single pill combination (SPC) group (70.69% vs vildagliptin + metformin 55.42%). Multi-variate logistic regression analysis showed that disease duration (P < 0.0001), baseline HbA1c (P < 0.0001) and drug administrative type (P = 0.0103) had significant impact on the effectiveness of the drug. Conclusion: In routine clinical practice in South Korea, vildagliptin+metformin could be considered as an effective treatment option for patients with T2DM.