OBJECTIVES: To assess the risk of hospitalization for trauma associated with use of hypoglycemic glucose-lowering drugs (GLDs) in individuals aged 65 and older. DESIGN: Observational, nested, case-control study. SETTING: The Echantillon Generaliste de Beneficiaires claims database, a 1/97(th) representative sample of the population covered by French healthcare insurance. PARTICIPANTS: All persons with a first hospitalization for trauma between 2009 and 2015 were considered as potential cases. They were selected if they had been followed for 365 days or longer at index date, were aged 65 and older, and had no diagnosed cancer. Cases (n=10,743) were matched with up to 10 randomly selected controls on age, sex, and length of follow-up (n=106,629). MEASUREMENTS: GLD exposure was considered globally and according to use of hypoglycemic GLDs alone, nonhypoglycemic GLDs alone, or both types of GLDs. Risk of hospitalization for trauma was estimated using hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Risk of hospitalization for trauma was significantly higher with use of GLDs (HR=1.15, 95% CI=1.08-1.22). Greater risk was found only in individuals treated with hypoglycemic GLDs alone (HR=1.26, 95% CI=1.15-1.38), particularly insulin (HR=1.49, 95% CI=1.32-1.68) and glinides (HR=1.34, 95% CI=1.12-1.61). CONCLUSION: This study highlights the excess risk of serious trauma with the use of insulin and glinides.