Few studies have investigated the association between iodine status, thyroid disease, and cancer risk despite evidence that thyroid function impacts many organs, including the prostate. We investigated iodine status and prostate cancer risk prospectively using data from the NHANES I Epidemiologic Follow-up Study. Participants were stratified into tertiles according to the urinary iodine/creatinine ratio, as a marker of iodine exposure. As iodine is an integral constituent of thyroid hormones, we also examined the relationship between thyroid disease and prostate cancer risk. Relative to the group with low urinary iodine, the age-adjusted hazard ratio was higher (although marginally insignificant) in the moderate group, hazard ratio 1.33 (95% confidence interval 1.00-1.78), and significantly lower in the high group, 0.71 (0.51-0.99). Thyroid disease was associated with an increased prostate cancer risk, 2.34 (1.24-4.43). Similarly, > 10 yr since thyroid disease diagnosis was associated with an elevated risk, 3.38 (1.66-6.87). After adjusting for other confounding factors, only a history of thyroid disease, 2.16 (1.13-4.14), and > 10 yr since diagnosis of thyroid disease, 3.17 (1.54-6.51) remained significant. Although the role of dietary iodine remains speculative, a role for thyroid disease and/or factors contributing to thyroid disease as a risk factor for prostate carcinogenesis warrants additional investigation.