The association between oral and systemic disease continues to be elucidated, expanding from periodontal disease and cardiovascular disease risk to include endodontic infection and diabetes. The purpose of this study was to determine whether diabetic control, as measured by hemoglobin A1c, has a direct relationship with the size of periapical lesions as measured through cone beam CT imaging at the time of follow-up examination. 100 patients who received appropriate root canal treatment (as determined radiographically) two to four years prior in the Postgraduate Endodontics Clinic were recruited through phone calls and a mailed letter. All had periapical lesions at the time of initial diagnosis. Following informed consent, standard recall examination and periapical radiographs were completed. Then, blood was drawn for hemoglobin A1c (HbA1c) analysis and CBCT images were exposed. Measurement of the largest diameter in any direction of the lesion was determined by two experienced endodontists who were masked to the diabetic status or HbA1c levels of the patients. Statistical analysis was completed with Pearson correlation, as well as ANOVA and multiple regression analysis. 29 patients consented to participate. Two patients were excluded, as the treated teeth had been previously extracted. A significant positive correlation was found between the HbA1c and lesion size (r = 0.375, p = 0.027). Blood glucose level, as measured by Hemoglobin A1c, demonstrated a direct association with periapical lesion size at the time of recall.