ImportanceHead and neck cancers (HNC) impose a significant economic burden on healthcare systems. Understanding the direct medical costs across different phases of care is crucial for resource allocation and cost-effectiveness evaluations, particularly in universal healthcare settings.ObjectiveTo quantify the direct medical costs of HNC over 60 months postdiagnosis and examine cost variations by cancer subsite, stage, and treatment modality.DesignPopulation-based, matched case-control study using administrative healthcare data.SettingOntario, Canada, a province with a publicly funded universal healthcare system.ParticipantsWe included 19,832 adults diagnosed with HNC between 2007 and 2020. Each case was matched with 5 noncancer controls based on age, sex, and comorbidity.ExposuresHNC diagnosis, categorized by cancer subsite, stage, and treatment modality.Main Outcome MeasuresMean per-person direct medical costs attributable to HNC over a 63-month period, analyzed by phase of care, cancer subsite, stage, and treatment modality.ResultsThe mean per-person cost attributable to HNC over 63 months was $53,812.9 ± $762.2. Costs peaked in the first 3 months postdiagnosis ($9709.7 ± $36.1 per month) and declined over time. Larynx/hypopharynx cancers incurred the highest costs across most phases. Advanced-stage cancers were associated with increased costs, with stage IV cancers nearly doubling the costs of stage I. Multimodal treatments, particularly surgery combined with chemoradiation, resulted in the highest costs across all phases ( < .01).ConclusionsHNC results in substantial healthcare costs, with significant variations by subsite, stage, and treatment modality. The highest costs occur in the early treatment phase and remain elevated for patients requiring multimodal therapies.RelevanceThese findings provide critical data for policymakers and health system authorities to optimize resource allocation and assess cost-effectiveness. Future research should explore indirect costs and the impact of early detection strategies to reduce the economic burden of HNC.Level of evidence3.