Black patients are reported to have a higher incidence of advanced disease and increased mortality from head and neck squamous cell carcinoma (HNSCC) but constitute the minority of patients in large-scale studies investigating the effect of race on outcome. This study sought to determine if racial disparities exist between black and white patients with HNSCC treated at a single large institution in the South with a high proportion of black patients. The authors conducted a nonrandomized retrospective cohort analysis. The tumor registry was used to identify patients diagnosed with HNSCC from 1985 to 2002. The medical records of non-Hispanic white and black adult patients were retrospectively reviewed. Median household income, percentage of population below poverty level, and education level based on census tract and block information were obtained from U.S. Census 2000 data. Standard statistical analysis, including Kaplan-Meier survival curve analysis and Cox proportional hazards models, was used to analyze the effects of covariables on survival. A total of 1,128 patients met study criteria (478 black, 650 white). Compared with white patients, black patients were significantly younger (mean age, 53.9 vs. 56.4 years, P<.0001), male (81.2% vs. 72.3%, P=.0005), more commonly abused alcohol (88.0% vs. 74.3%, P<.0001), and were significantly less likely to have insurance (8.6% vs. 21.7%, P<.0001). There was no difference in the incidence of tobacco use (91.7%), advanced comorbidity (35.9%), or primary tumor site. Black patients had a significantly greater incidence of stage IV disease (65.7% vs. 46.6%, P<.0001) and nonoperative treatment (48.7% vs. 30.8%, P<.0001), which was performed for inoperable disease in 57.1% of black compared with 31.0% of white patients (P<.0001). Black patients resided in census block groups with significantly lower mean education level, median income, and a higher percentage of population below poverty compared with white patients. The 5-year disease-specific survival differed significantly between black (29.3%) and white (54.7%) patients (P<.0001). Cox proportional hazards models revealed that alcohol abuse, advanced TNM stage, high tumor grade, nodal disease, extracapsular spread, advanced comorbidity, and regional or distant metastatic disease were associated with poorer survival for all patients. An interaction with race was found for insurance status, nonoperative treatment, and extracapsular spread. Stepwise variable selection adjusting for patient, tumor, and treatment characteristics showed a significant effect only for race by payor status on disease-specific survival (P=.0228). Insurance status, treatment, and extracapsular spread differentially affected the survival of black patients compared with white patients. Only insurance status had a significant effect on survival in black patients after controlling for other variables. These data suggest that racial differences in HNSCC outcomes are primarily related to differences in access to health care.