Abstract Background: Hyperglycemia may increase the risk of colorectal neoplasia by serving as an energy source for neoplastic growth. We sought to determine whether glycemic control measured by serial hemoglobin A1c (HbA1c) was associated with the risk of colorectal adenoma. Methods: Among a cohort of patients with type 2 diabetes mellitus who received health care within the Kaiser Permanente Northern California from 1994 to 2005, we conducted 2 case–control analyses. Cases had at least 1 colorectal adenoma identified at either colonoscopy (analysis 1) or sigmoidoscopy (analysis 2). Controls had no colorectal neoplasia identified at the corresponding endoscopic examination. Serial HbA1c levels between the cases and the controls were compared using a longitudinal model. Results: Case–control analysis 1 included 4,248 patients, of whom 1,296 (31%) had at least 1 adenoma. The adjusted mean HbA1c levels among those without any adenomas was 8.20% versus 8.26% among those with at least 1 adenoma, a difference of 0.06% (95% CI = −0.02 to 0.14, P = 0.16). Case–control analysis 2 included 9,813 patients, of whom 951 (10%) had at least 1 distal adenoma. The adjusted mean HbA1c levels among those without any distal adenomas was 8.32% versus 8.37% among those with at least 1 distal adenoma, a difference of 0.05% (95% CI = −00.04 to 0.14, P = 0.25). The results were similar for advanced adenomas. Conclusions: Glycemic control was not associated with the risk of colorectal adenoma among diabetic persons. Impact: These results would suggest that glycemic control is unlikely to confound the reported association between diabetes medications and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 19(12); 3027–36. ©2010 AACR.