OBJECTIVE To evaluate the effect of orbital steroid injections in patients with active thyroid ophthalmopathy resistant to or dependent on systemic steroids, or with complications related to systemic steroid use. METHODS This prospective non-comparative case series includes 31 eyes of 17 patients with active thyroid ophthalmopathy and clinical activity score (CAS) of 3 or more, without compressive optic neuropathy or overt exposure keratopathy. All subjects had a history of previous systemic steroid use (with steroid resistance or dependence) or had developed complications related to steroids. A combination of steroids including triamcinolone acetonide 20 mg and dexamethasone 4 mg was injected in the upper and lower retroseptal orbital spaces three or four times at one-month intervals. The patients were examined periodically after each injection and at least three months after the last injection. RESULTS Mean pre-injection CAS was 5.2 1.3 which was improved to 1.6 1 after the fourth injection (P 0.001). Upper and lower lid retraction improved in 100% and 68.2% of the affected eyes, respectively. Strabismus completely resolved in one of five affected patients and the most significant improvement was observed in supraduction. Mean improvement in exophthalmos was 1.2 1.1 mm. Visual acuity did not significantly change after the injections. Eyelid ecchymosis and/or subconjunctival hemorrhage was observed in 7.1% and intraocular pressure rise occurred in 8.8% of eyes. CONCLUSIONS Orbital steroid injections can be used for the treatment of active thyroid ophthalmopathy when the patient is resistant to or dependent on systemic steroids or has developed complications of systemic steroids.