AIM: To evaluate the efficacy and safety of orbital decomposition (OD) surgery in combination with horse chestnut seed extract (HCSE), as compared to OD alone, in patients with thyroid-associated ophthalmopathy (TAO). METHODS: Sixty-two orbits from 62 TAO patients were randomly assigned to OD or OD+HCSE at 1:1 ratio (31 received OD alone, 31 received OD+HCSE). Forty-two orbits from 21 healthy subjects were used as controls. Complete ophthalmic examination and color Doppler flow imaging (CDFI) were performed before surgery and 3mo post-surgery on all 62 orbits from the TAO patients. CDFI were also performed on the 42 control orbits. The effect of OD+HCSE and OD alone on TAO orbits was compared on several endpoints, including superior ophthalmic vein blood flow (SOVBF) parameters, subjective assessment, soft tissue involvement, lid retraction, diplopia, eye movement restriction, degree of exophthalmos, and intraocular pressure. The control orbits were used as reference for the SOVBF parameters. RESULTS: OD surgery with or without HCSE improved SOVBF, symptoms and soft tissue involvement, decreased degree of exophthalmos and intraocular pressure in orbits of TAO patients. The OD+HCSE combination led to significantly better improvement of SOVBF than OD alone. The differences between the reductions of SOVBF in the two groups are 1.26 cm/s in max-volecity and 0.52 cm/s in min-volecity (P<0.0001). CONCLUSION: SOVBF is significantly reduced in the orbits affected with TAO, indicating that congestion may be an important factor contributing to TAO pathogenesis. OD surgery improves the SOVBF, and combination of HCSE medication and OD surgery further improved venous return than OD surgery alone.