Background: Diabetes is associated with cancer risk in the aging population. Observational studies have indicated the beneficial effects of metformin against breast cancer, making studies on the anticancer potential of antidiabetic drugs worthwhile. This study investigated cancer incidence in patients on antidiabetic monotherapy. Methods: Using National Health Insurance Service data (2002-2013), a retrospective cohort study that included type 2 diabetes mellitus (T2DM) patients was conducted. Study subjects were enrolled if they were ${\geq}30$ years old, on monotherapy for diabetes, and cancer-free. They were followed up for cancer occurrence or death, until December 31st, 2013. A Cox proportional hazard model analysis was conducted between metformin and sulfonylurea (including meglitinide) users, to determine cancer risk, with adjustment for age, gender, comorbidity index, dyslipidemia, hypertension, and T2DM duration. Results: The number of antidiabetic monotherapy-treated T2DM patients without a history of cancer was 9,554 (metformin, n = 5,825; sulfonylurea, n = 3,225; others, n = 504). During the follow-up period (mean, 2.04; IQR, 3.18 years), the cancer incidence rate was 5.48/100 and 5.45/100 patient-years for metformin and sulfonylurea, respectively. The hazard ratio (HR) for risk of cancer incidence in the metformin group was 0.74 (95% confidence interval [CI], 0.66-0.83; p < 0.0001), compared with sulfonylurea. Additionally, the HRs for risks of lung, liver, and stomach cancer were respectively 0.46 (95% CI, 0.31-0.66; p < 0.0001), 0.41 (95% CI, 0.31-0.54; p < 0.0001), and 0.51 (95% CI, 0.35-0.73; p = 0.0003). Conclusion: Antidiabetic therapy with metformin reduces cancer risk by 26%, specifically for lung, liver, and stomach cancer.