Background: Diabetes mellitus (DM) is associated with increased risk of colon cancer and has potential impact on its prognosis. This study aimed to investigate the association between DM and the prognosis of patients with early colon cancer who underwent curative surgery. Methods: We established the patient cohort of the study by searching the database of the population-based Taiwan National Cancer Registry. All patients who had newly diagnosed stage I or II colon cancer from 2004 to 2007 and underwent surgical resection with uninvolved surgical margins were enrolled. Information of DM, anti-DM medication, and other comorbidities was retrieved from the database of National Health Insurance, Taiwan. Colon cancer-specific survival (CSS) and overall survival (OS) were compared between patients with and without DM. The Cox proportional hazard model was used to estimate the adjusted hazard ratio (HR) of clinicopathologic variables in multivariate analysis. Results: A total of 5,525 patients were identified; 1,009 of them (18.9%) had DM and 4,325 of them (81.1%) had no DM. Patients with DM had an older median age at diagnosis (69.9 y vs. 66.8 y, p < 0.001), similar initial stage and grade, fewer adjuvant chemotherapy (26.5% vs. 31.2%, p = 0.003). Patients with DM had significantly poorer CSS and OS than patients without DM (Table). In multivariate analysis adjusting for age, gender, stage, adjuvant chemotherapy and comorbidities, DM remained an independent prognostic factor for poorer OS (adjusted HR: 1.45, p < 0.001). Among patients with DM, patients who used insulin had significantly poorer CSS and OS than patients who did not (5-year CSS: 79.5% vs. 85.5%, p = 0.047; 5-year OS: 50.9% vs. 70.4%, p < 0.001). Conclusions: In patients receiving curative surgery for early colon cancer, patients with DM had poorer OS than patients without DM.