Objective: To observe the clinical efficacy of medial-inferior wall orbital decompression combined with fat decompression in the treatment of moderate-to-severe thyroid associated ophthalmopathy (TAO). Methods: A retrospective analysis was performed on 25 patients (31 eyes) with moderate-to-severe TAO from January 2020 to January 2022 in Eye Hospital of Zhejiang University, who were treated with medial-inferior wall orbital decompression combined with fat decompression. All of patients were given orbital computed tomography to measure visual acuity, exophthalmos, diplopia and ocular appearance before operation. The preoperative and postoperative exophthalmos, visual acuity and diplopia before and after operation were taken as efficacy evaluating indicators. The related data was counted and analyzed statistically. Results: After operation, the reduction of exophthalmos was 2-6 mm, with an average of (3.45±0.93) mm, the volume of intrazonal fat-removal was 1.4-3.6 mL, with an average of (2.33±0.66) mL, with a satisfactory appearance. There were 4 cases of preoperative diplopia and 2 cases of new diplopia after operation, all of which were mild diplopia. Diplopia did not exacerbate after operation in the patients who had diplopia before operation. Conclusion: Medial-inferior wall orbital decompression combined with fat decompression in the treatment of moderate-to-severe TAO can effectively expand orbital volume, reduce exophthalmos, improve appearance with a concealed beautiful surgical incision, showing its good clinical efficacy.