Background. The authors used a custom-built electronic record system to investigate endodontic diagnostic and treatment outcome data in patients with and without diabetes. Methods. The medical histories and endodontic treatment data for nonsurgical endodontic patients treated in predoctoral and postgraduate specialty clinics were entered into an electronic record system. A total of 5,494 cases (including 284 cases in patients with diabetes) were treated, and 540 cases (including 73 cases in patients with diabetes) had follow-up data two years or more postoperatively. The authors performed univariate and multivariate analyses to determine important factors affecting endodontic diagnosis and treatment outcome. Results. Patients with diabetes had increased periodontal disease of teeth with endodontic involvment compared with patients who did not have diabetes. There was a trend toward increased symptomatic periradicular disease in patients with diabetes who received insulin, as well as flare-ups in all patients with diabetes. Two years or longer postoperatively, 68 percent of cases followed were successful. Older age, the absence of preoperative lesions, the presences of permanent restorations and longer postoperative evaluation periods all were associated with a successful outcome. A multivariate analysis showed that in cases with preoperative periradicular lesions, a history of diabetes was associated with a significantly reduced successful outcome. Conclusions. Patients with diabetes have increased periodontal disease in teeth involved endodontically and have a reduced likelihood of success of endodontic treatment in cases with preoperative periradicular lesions. Clinical Implications. Patients with diabetes who are treated endodontically should be assessed carefully and be treated with effective antimicrobial root canal regimens, particularly in cases with preoperative lesions.