Abstract Background: Emerging evidence from cohort studies indicates that adiposity is associated with greater incidence of head and neck cancer. However, most studies have used self-reported anthropometry which is prone to error. Methods: Among 363,094 participants in the European Prospective Investigation into Cancer and Nutrition study (EPIC) with measured anthropometry, there were 837 incident cases of head and neck cancer. Head and neck cancer risk was examined in relation to body mass index (BMI) [lean: <22.5 kg/m2, normal weight (reference): 22.5–24.9 kg/m2, overweight 25–29.9 kg/m2, obese: ≥30 kg/m2], waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) using Cox proportional hazards models. Results: Among men, a BMI < 22.5 kg/m2 was associated with higher head and neck cancer risk [HR 1.62; 95% confidence interval (CI), 1.23–2.12)]; BMI was not associated with head and neck cancer among women. WC and WHR were associated with greater risk of head and neck cancer among women (WC per 5 cm: HR, 1.08; 95% CI, 1.02–1.15; WHR per 0.1 unit: HR, 1.64; 95% CI, 1.38–1.93). After stratification by smoking status, the association for WHR was present only among smokers (Pinteraction = 0.004). Among men, WC and WHR were associated with head and neck cancer only upon additional adjustment for BMI (WC per 5 cm: HR 1.16; 95% CI, 1.07–1.26; WHR per 0.1 unit: HR, 1.42; 95% CI, 1.21–1.65). Conclusions: Central adiposity, particularly among women, may have a stronger association with head and neck cancer risk than previously estimated. Impact: Strategies to reduce obesity may beneficially impact head and neck cancer incidence. Cancer Epidemiol Biomarkers Prev; 26(6); 895–904. ©2017 AACR.