Importance: Risk factors for in-hospital mortality of patients with head and neck cancer (HNC) are multilevel. Studies have examined the effect of patient-level characteristics on in-hospital mortality; however, there is a paucity of data on multilevel correlates of in-hospital mortality. Objective: To examine the multilevel associations of patient- A nd hospital-level factors with in-hospital mortality and develop a nomogram to predict the risk of in-hospital mortality among patients diagnosed with HNC. Design, Setting, and Participants: This cross-sectional study used the 2008-2013 National Inpatient Sample database. Hospitalized patients 18 years and older diagnosed (both primary and secondary diagnosis) as having HNC using the International Classification of Diseases, Ninth Revision, Clinical Modification codes were included. Analysis began December 2018. Main Outcomes and Measures: The primary outcome of interest was in-hospital mortality. A weighted multivariable hierarchical logistic regression model estimated patient- A nd hospital-level factors associated with in-hospital mortality. Moreover, a multivariable logistic regression analysis was used to build an in-hospital mortality prediction model, presented as a nomogram. Results: A total of 85440 patients (mean [SD] age, 62.2 [13.5] years; 61281 men [71.1%]) were identified, and 4.2% (n = 3610) died in the hospital. Patient-level risk factors associated with higher odds of in-hospital mortality included age (adjusted odds ratio [aOR], 1.03 per 1-year increase; 95% CI, 1.02-1.03), male sex (aOR, 1.23; 95% CI, 1.12-1.35), higher number of comorbidities (aOR, 1.14; 95% CI, 1.11-1.17), having a metastatic cancer (aOR, 1.49; 95% CI, 1.36-1.64), having a nonelective admission (aOR, 3.26; 95% CI, 2.83-3.75), and being admitted to the hospital on a weekend (aOR, 1.30; 95% CI, 1.16-1.45). Of the hospital-level factors, admission to a nonteaching hospital (aOR, 1.48; 95% CI, 1.24-1.77) was associated with higher odds of in-hospital mortality. The nomogram showed fair in-hospital mortality discrimination (area under the curve of 72%). Conclusions and Relevance: This cross-sectional study found that both patient- A nd hospital-level factors were associated with in-hospital mortality, and the nomogram estimated with fair accuracy the probability of in-hospital death among patients with HNC. These multilevel factors are critical indicators of survivorship and should thus be considered when planning programs or interventions aimed to improve survival among this unique population.