BACKGROUND: Although patients with cancer generally respond favorably to vaccination, they may not receive annual influenza vaccinations. The current population-based study described the epidemiology and outcomes of potentially preventable, serious influenza-related infections in patients with cancer. METHODS: From the Nationwide Inpatient Sample, the authors created a subsample that included discharges with any International Classification of Diseases, ninth revision, diagnosis code for cancer and principal diagnosis code for influenza, bronchopneumonia, or pneumonia caused by an unspecified organism. From the latter two diagnosis codes, the authors estimated excess cases during the influenza season for each year and stratum, then selected a random sample from fall and winter discharges. Subset analyses included weighted sample means, frequencies, and analysis of variance values. The authors converted charges to costs using cost-to-charge ratios and inflated these to 2003 U.S. dollars. Hospitalization and mortality rates were calculated using 5-year cancer prevalence estimates. RESULTS: The estimated mean annual hospital discharges of patients with cancer with potentially preventable, serious influenza-related infections numbered 16,000. The average length and cost per stay were 6 days and > $6300, respectively. Approximately 9% of patients died in the hospital and 31% needed further skilled care. The estimated age-specific rates for hospitalization and death per 100,000 in the prevalent cancer population were 219 and 17.4, respectively, for patients age < 65 years and 623 and 59.4, respectively, for those age >/= 65 years. Hospitalization costs averaged $1300 more for patients age < 65 years. CONCLUSIONS: Death from influenza-related infections occurred in an estimated 9% of patients with cancer hospitalized for such. Using recommended vaccination schedules for patients with cancer and their contacts reduced hospitalizations, treatment delays, and deaths in this highly susceptible population.