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To understand measures of frailty among preoperative patients and explain how these can predict perioperative outcomes among patients with head and neck cancer.Retrospective cross-sectional case series with chart review.Academic tertiary medical center.A retrospective review was performed of patients presenting to an academic hospital following a surgical procedure for a head and neck cancer diagnosis. Charts were queried for preoperative medical diagnoses to calculate 2 frailty scores: the American College of Surgeons National Surgical Quality Improvement Program modified frailty index and the Johns Hopkins Adjusted Clinical Groups frailty index. The American Society of Anesthesiologists classification system was also analyzed as a predictor. Primary outcomes were mortality, 30-day readmission, and length of stay. Perioperative complications and discharge disposition were also evaluated.A total of 410 charts were queried between January 2014 and December 2017. Mortality was 11%; mean ± SD length of stay was 7.4 ± 5.5 days; and the readmission rate was 17%. The modified frailty index score significantly increased the odds of mortality (odds ratio = 1.475, P = .012) and readmission (odds ratio = 1.472, P = .004), the length of stay (relative risk = 1.136, P = .001), and the number of perioperative complications. The American Society of Anesthesiologists classification was also significantly associated with poor outcomes, including readmission, length of stay, and perioperative complications. The Adjusted Clinical Groups index was not a significant predictor of outcomes in this study population.This study demonstrated a significant increase in poor perioperative outcomes and mortality among patients with head and neck cancer and increased frailty, as measured by the modified frailty index.