In order to investigate the relationship between Graves disease, its associated ophthalmopathy and smoking, we followed retrospectively a group of 270 patients with Graves disease (233 females and 37 males). Smoking incidence within this group was compared to that found in a control, thyroid disease-free group of 120 patients. The incidence of smokers was significantly higher in the group with Graves disease (145 out of 270, 54%) when compared to the control group (42 out of 120, 35%, P<0.01). The 143 patients with Graves disease having clinically obvious ophthalmopathy included a higher percentage of smokers than those without significant ophthalmopathy (63% compared to 43%, P<0.01). This difference was due mainly to female patients (76 smokers out of 123 female patients with ophthalmopathy 62%, compared to only 44 smoking ophthalmopathy-free Graves patients out of 109 −40%, P<0.001). Forty-four out of 90 (49%) tobacco users having ophthalmopathy were heavy smokers (i.e. over one pack per day for over 20 years), an incidence significantly higher than that of heavy smokers found in the smoking Graves patients without ophthalmopathy (19 out of 55, 35%), or in the smoking patients from the control group (13 out of 42, 31%) (P<0.05). The data obtained support the hypothesis of tobacco influence upon Graves disease evolution. Smoking seems to trigger both thyroid disease and ophthalmopathy appearance, especially in females. The risk of ophthalmopathy development and its severity might be dependent of the amount of cigarettes smoked.