We wondered whether the relapse rate of Graves' hyperthyroidism was increased amongst patients who smoked. To this end, a retrospective analysis of clinical and laboratory data of consecutive patients with Graves' disease was carried out. All patients were treated with thionamide anti-thyroid drugs (ATD) for at least one year and remission was defined as continued and biochemical euthyroidism, at least 6 months after discontinuing ATD. The study comprised 221 subjects with Graves' disease from a hospital-based population over 9 years. We took the following variables into account when assessing contribution to disease relapse: Goiter, Thyroid Associated Ophthalmopathy (TAO), and Time to euthyroidism after starting ATD and interaction between smoking and sex. Smoking had a marginally significant (p=0.081) deleterious effect on the likelihood of remission after ATD treatment for Graves' disease. The effect of smoking was, however, highly significant in males and indeed the deleterious effect on remissions may be restricted to males (odds ratio, 11.1; 95% confidence interval, 1.25 to 98.5). The presence of goiter (odds ratio, 3.8; 95% confidence interval, 2.05 to 7.1) and TAO (odds ratio, 1.8; 95% confidence interval, 0.993 to 3.18) forecasted lower chances of achieving remission. The shorter the time a patient became euthyroid after starting ATD the more likely his disease was to remit. We conclude that cigarette smoking increases the likelihood of Graves' disease recurrence in males treated with anti-thyroid drugs. Thus, smoking appears to be an important risk factor in the pathogenesis and outcome of Graves' disease patients at least in subsets of patients.