Diets eliminating animal products have rarely been associated with hypothyroidism but may protect against autoimmune disease. Thus, we investigated whether risk of hypothyroidism was associated with vegetarian compared to omnivorous dietary patterns. The Adventist Health Study-2 was conducted among church members in North America who provided data in a self-administered questionnaire. Hypothyroidism was queried at baseline in 2002 and at follow-up to 2008. Diet was examined as a determinant of prevalent (n = 4237 of 65,981 [6.4%]) and incident cases (1184 of 41,212 [2.9%]) in multivariate logistic regression models, controlled for demographics and salt use. In the prevalence study, in addition to demographic characterstics, overweight and obesity increased the odds (OR 1.32, 95% CI: 1.22–1.42 and 1.78, 95% CI: 1.64–1.93, respectively). Vegan versus omnivorous diets tended to be associated with reduced risk (OR 0.89, 95% CI: 0.78–1.01, not statistically significant) while a lacto-ovo diet was associated with increased risk (OR 1.09, 95% CI: 1.01–1.18). In the incidence study, female gender, white ethnicity, higher education and BMI were predictors of hypothyroidism. Following a vegan diet tended to be protective (OR 0.78, 95% CI: 0.59–1.03, not statistically significant). In conclusion, a vegan diet tended to be associated with lower, not higher, risk of hypothyroid disease.