The purpose of this study was to assess alterations in fracture risk in patients with hyper- and hypothyroidism, and the effects of antithyroid drugs and levothyroxine on fracture risk. The study was designed as a case-control study. All patients with a fracture (n = 124,655) in the year 2000 in Denmark served as cases. For each case, three age- and gender-matched controls were randomly drawn from the general population (n = 373,962). Exposure variables were a diagnosis of hyperthyroidism, hypothyroidism, ever use of antithyroid drugs, and ever use of levothyroxine. Adjustments were made for time since diagnosis, surgery for hyperthyroidism, thyroid cancer, prior fracture, alcoholism, and corticosteroid use. There was an increase in the risk of any fracture within the first 5 years after a diagnosis of hyperthyroidism, and the first 10 years after a diagnosis of hypothyroidism. Use of antithyroid drugs was associated with a significantly reduced fracture risk independently of the dose used (odds ratio [OR] 0.79-0.84, 2P < 0.05). No effect of levothyroxine on fracture risk was present. Thyroid surgery for hyperthyroidism and thyroid cancer were not associated with fracture risk. A prior fracture, alcoholism, and corticosteroid use were significant risk factors for fractures. Fracture risk is increased at the time of diagnosis of both hyper- and hypothyroidism, and this increase seems reversible. Low-dose levothyroxine was not associated with fracture risk. The effect of antithyroid drugs may be caused by the reduction in thyroid hormone levels.