Background: Thyroid cancer incidence has risen dramatically in the United States since the early 1980s. Although the prevalence of obesity has doubled during this time period, the relationship between obesity and thyroid cancer is uncertain. Methods: We examined the association between body mass index (BMI) and thyroid cancer risk in a pooled analysis of five prospective U.S. studies, including 413,979 women and 434,953 men. Proportional hazards models with attained age as the time metric were adjusted for education, race, marital status, smoking, alcohol intake, and (where appropriate) cohort and sex. Results: Over follow-up (mean = 10.3 years), 768 women and 388 men were diagnosed with thyroid cancer. The risk of thyroid cancer was greater with increasing BMI [per 5 kg/m2: HR in women, 1.16 (95% CI, 1.08-1.24); HR in men, 1.21 (95% CI, 0.97-1.49)]. There was no significant heterogeneity between studies (both P > 0.05). For women and men combined, the HRs for overweight (25.0-29.9 kg/m2) and obesity (≥30 kg/m2) compared with normal-weight (18.5-24.9 kg/m2) were 1.20 (95% CI, 1.04-1.38) and 1.53 (95% CI, 1.31-1.79), respectively. We found no significant effect modification by other factors, and the results did not differ significantly by histologic type. A significant positive association for BMI in young adulthood (ages 18-20) with thyroid cancer risk was also observed [per 5-kg/m2 increase: HR, 1.18 (95% CI, 1.03-1.35)]. Conclusion: BMI was positively associated with thyroid cancer risk in both men and women. Impact: Our study provides strong evidence that obesity is an independent risk factor for thyroid cancer. ©2011 AACR.