Body mass index (BMI) has been positively associated with thyroid cancer risk in several studies, but the underlying mechanisms remain unclear. We examined the associations for waist and hip circumference and weight change during adulthood with thyroid cancer risk among 125,347 men and 72,363 women in the NIH-AARP Diet and Health Study who completed a second mailed questionnaire in 1996–1997. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated separately by sex and adjusted for race/ethnicity, education and smoking status. During follow-up (median = 10.1 years), 106 men and 105 women were diagnosed with a first primary thyroid cancer, as identified through linkage to state cancer registries. Having a large waist circumference (above the clinical cutpoint for normal: >102 cm in men and >88 cm in women) was associated with increased risk in both men (HR = 1.79, 95% CI: 1.21–2.63) and women (HR = 1.54, 95% CI: 1.05–2.26). Having both a large waist and BMI in the obese range (≥30 kg/m2) approximately doubled the risk of thyroid cancer (HR in men = 2.13, 95% CI: 1.18–3.85; HR in women = 1.91, 95% CI: 1.31–3.25) compared to having a normal waist circumference/normal BMI (18.5–24.9 kg/m2). We also observed positive association for weight gain between ages 18–35 in men (gained ≥10.0 kgvs. lost/gained <5 kg, HR = 1.49, 95% CI: 0.93–2.39,p-trend = 0.03), but the association was less pronounced in women. No clear association for weight gain in later life was observed. These results support a potential role for hormonal and metabolic parameters common to central adiposity in thyroid carcinogenesis.