AIM: To evaluate the efficacy of combined orbital radiation and periorbital triamcinolone acetonide injection for patients with Graves’ orbitopathy (GO) who experienced treatment failure with glucocorticoid pulse therapy (GPT). METHODS: A total of 57 eligible patients (35.09% males, mean age of 51.19±11.90y) were included in this case-series study. The medical information collected during each visit was evaluated and analyzed. RESULTS: Significant improvement was observed in patients six months after radiation therapy. Both the clinical activity score and the efficacy score showed substantial improvement (P<0.001). Furthermore, there was significant resolution of extraocular muscle inflammation on magnetic resonance imaging at three and six months after radiation therapy. The initial high signal intensity ratio (SIR) max was found to be associated with greater improvement in SIR sum (P<0.001, B=2.002, 95%CI: 1.377 to 2.628), while the presence of sight-threatening stage or moderate to severe diplopia negatively influenced the improvement of SIR sum (P=0.045, 0.008, 0.006; B=-1.966, -1.478, -0.997; 95%CI: -3.886 to -0.045, -2.552 to -0.403, -1.694 to -0.300; respectively). CONCLUSION: The combination therapy demonstrates significant effectiveness in treating patients with GO who experienced severe ocular inflammation and have previous GPT failure. Noticeable improvement is observed as early as one month after initiating radiation therapy, and patients with more severe inflammatory states showes greater benefit from the treatment.