A nested case-control study was carried out using data from the United States Department of Defense cohort between 2000 and 2013 to investigate the associations of papillary thyroid cancer (PTC) with serum concentrations of polybrominated diphenyl ethers and polybrominated biphenyls. This study included 742 (341 women and 401 men) histologically confirmed PTC cases and 742 matched controls with pre-diagnostic serum samples from the Department of Defense Serum Repository. Lipid-corrected serum concentrations of eight congeners were measured. Multivariate conditional logistic regression analyses were performed for classical PTC and follicular variant of PTC, respectively. We also examined effect modification by gender. BDE-28 was associated with significantly increased risk of classical PTC [OR=2.09; 95% CI, 1.05, 4.15, for the 3rd tertile vs. below limit of detection; Ptrend=0.02], adjusting for other congeners, body mass index, and branch of military service. This association was mainly observed for larger classical PTC (tumor size >10 mm) with a significantly stronger association among women than men (Pinteraction=0.004). No consistent associations were observed for other congeners, including those at higher concentrations. This study found a significantly increased risk of classical PTC associated with increasing levels of BDE-28. The risk varied by gender and tumor size. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2019.