Objective The impact of diabetes mellitus (DM) on surgical outcomes and cost of care for patients undergoing surgery for head and neck cancer (HNCA) is not well established. We used the Nationwide Inpatient Sample to analyze the postoperative impact of DM on HNCA patients. Study Design Population-based inpatient registry analysis. Setting Academic medical center. Subjects and Methods Discharge data from the Nationwide Inpatient Sample were analyzed for patients undergoing HNCA surgery from 2002 to 2010. Patient demographics, comorbidities, length of stay, hospital charges, and postoperative complications were compared between HNCA patients with and without DM. Results Of 31,075 patients, 4029 patients (13.0%) had a DM diagnosis. DM patients were older (65.7 10.8 vs 61.1 +/- 14.1 years old; P < .001), had more preexisting comorbidities, had longer hospitalizations, and incurred greater hospital charges. Compared with the non-DM cohort, DM patients experienced significantly higher rates of postoperative infections (2.6% vs 2.1%, P = .025), cardiac events (9.0% vs 4.3%, P < .001), pulmonary edema/failure (6.6% vs 5.7%, P = .023), acute renal failure (3.3% vs 1.5%, P < .001), and urinary tract infections (2.8 % vs 2.1%, P = .005). No differences in surgical wound healing rates were observed (0.1 vs 0.1, P = .794). On multivariate logistic regression corrected for age and race, DM patients had greater odds of postoperative infections (1.382, P = .007), cardiac events (1.893, P < .001), and acute renal failure (2.023, P < .001). Conclusions DM is associated with greater length of stay and hospital charges among HNCA patients. DM patients have significantly greater rates of postoperative complications, including postoperative infections, cardiac events, and acute renal failure.