We investigated the long-term side-effects of orbital radiotherapy (OR) in 204 patients with Graves' ophthalmopathy (GO), irradiated from 1972-1996 [44 by cobalt unit (CU) and 160 by linear accelerator (LA), mostly combined with glucocorticoids], with a 5- to 25-yr follow-up (median, 11 yr). Cataract was observed in 21 patients (10%) 3-21 yr after OR, with a higher (not significant) prevalence in CU-treated patients (18% vs. 8% in LA-treated patients). The prevalence of cataract was higher, although not significantly, in CU-treated patients aged less than 60 yr, but not in LA-treated patients, compared with the general population. Mild, asymptomatic retinopathy was observed in 1 of 7 patients (14%) with diabetes and hypertension, in 1 of 31 patients (3%) with hypertension alone, and in 0 of 11 patients with diabetes alone. No tumors were observed in 157 patients submitted to computed tomography scan of orbital and adjacent regions. In conclusion, OR is a safe treatment, not associated with an increased frequency of cataract, provided a high voltage apparatus is used. Hypertension, especially if associated with diabetes, may represent a relative contraindication, as it may cause retinopathy. Although no secondary tumors were detected, due to the long latency of radiation-induced tumors, OR should be restricted to patients older than 35 yr.