Abstract Objectives This noninterventional, multidatabase, analytical cohort study explored whether vildagliptin is associated with an increased risk of specific safety events of interest, namely angioedema, foot ulcers, or skin lesions, adverse hepatic events, or serious infections compared with other noninsulin antidiabetic drugs (NIADs) using real‐world data from five European electronic healthcare databases. Design Patients with type 2 diabetes mellitus aged ≥18 years on NIAD treatment were included between January 2005 and June 2014. Adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the outcomes of interest were estimated using negative binomial regression. Patients Approximately 2.8% of the included patients (n = 738 054) used vildagliptin at any time during the study, with an average follow‐up time of 1.4 years. Results The adjusted IRRs (vildagliptin vs. other NIADs) were in the range of 0.87‐3.71 (angioedema), 0.73‐1.19 (foot ulcers), 0.37‐1.18 (skin lesions), 0.24‐1.14 (composite of foot ulcer or skin lesions), 0.29‐0.55 (serious hepatic events), and 0.59‐1.04 (serious infections), with no lower bound of the 95% CIs > 1. Conclusions Overall, there was no increased risk of the events of interest in association with vildagliptin use compared with other NIADs.