ABSTRACT Introduction Vitamin B12 deficiency is one of the adverse drug reactions of metformin and proton pump inhibitors (PPIs). As symptoms of gastroesophageal reflux disease are frequently reported in patients with diabetes, the concomitant use of metformin and PPI is expected. Therefore, this study aimed to investigate the effects of concurrent PPI use on the risk of vitamin B12 deficiency in patients with type 2 diabetes (T2DM) using metformin. Materials and Methods This retrospective cohort study was conducted using a sample cohort database provided by the National Health Insurance Service. Among adult patients newly diagnosed with T2DM, new users of metformin who used metformin ≥4 months were included. The subjects were divided into two cohorts: metformin monotherapy and metformin + PPI. Vitamin B12 deficiency was defined by a diagnostic code or a prescription of medications for vitamin B12 supplementation. A Cox proportional hazards model was used to estimate the adjusted hazard ratio (aHR) with a 95% confidence interval (CI). Results In total, 11,200 subjects were included in the 1:1 propensity score‐matched cohort. The risk of vitamin B12 deficiency was significantly higher in the metformin + PPI cohort compared with the metformin monotherapy cohort (aHR, 1.18; 95% CI, 1.02–1.35). Conclusions A significant association between the concurrent use of metformin and PPI and an increased risk of vitamin B12 deficiency was found, highlighting the need to carefully monitor the symptoms associated with vitamin B12 deficiency and regularly assess vitamin B12 levels when considering the concomitant use of PPI and metformin.