OBJECTIVES: To assess healthcare resource utilization and economic burden associated with metastatic and recurrent, locally-advanced head and neck cancer (HNC). METHODS: Administrative claims from Medicare- and privately-insured individuals during 2004-2008 were used in this retrospective database study of patients with metastatic or recurrent, locally-advanced HNC.  Patients diagnosed with HNC were matched 1:1 to cancer-free control patients in order to measure the incremental economic burden of metastatic and recurrent, locally-advanced HNC.  Outcomes of interest were measured during the 6 months following 1) date of a secondary tumor diagnosis for metastatic patients, or 2) date of a diagnosis indicating recurrent, locally-advanced HNC.  The multivariable comparison of healthcare utilization rates was based on a logistic regression model.  Costs were reported in 2008 US dollars from the perspective of a third-party payer and were analyzed using generalized linear models and two-part regression models.  Regression models were adjusted for age and baseline Charlson Comorbidity Index (excluding cancer diagnoses) differences between HNC and control patients.  RESULTS:   The metastatic HNC cohort consisted of 1,042 patients; the cohort of recurrent, locally-advanced HNC included 324 patients.  Compared to cancer-free patients, a higher proportion of metastatic HNC patients had ≥ 1claim for inpatient (OR=26.4), outpatient (OR=35.3), and ER visits (OR=4.4).  Recurrent, locally-advanced HNC patients also had higher utilization rates for inpatient (OR=4.7) and ER visits (OR=4.9).  All differences were statistically significant (p<0.0001). Incremental adjusted total costs were $60,414 per patient for metastatic HNC and $21,141 per patient for recurrent, locally-advanced HNC (p<0.0001).  Approximately 46-58% of the incremental cost was attributable to outpatient visits, 27-37% to inpatient costs, and 11-13% to pharmacy, depending on the cohort. CONCLUSIONS:   Healthcare resource utilization and economic burden of patients with metastatic or recurrent, locally-advanced HNC is substantial compared to cancer-free patients.