Objective To investigate the effectiveness of endoscopic-assisted median nerve decompression with one-stage extensor indicis proprius (EIP) tendon transfer for reconstruction of thumb abduction in patients with severe carpal tunnel syndrome (CTS). Methods The clinical data of 12 patients with severe CTS who met the selection criteria between December 2019 and December 2024 were retrospectively analyzed. There were 2 males and 10 females with an average age of 55.4 years ranging from 35 to 67 years. The affected side was the right in 10 cases and the left in 2, with a mean symptom duration of 48.7 months (range, 12-120 months) and a mean thenar muscle atrophy duration of 13.4 months (range, 6-48 months). The median nerve was released with the help of endoscope, and the EIP tendon was transferred to reconstruct the abduction function of the thumb. The operation time and complications were recorded. Two-point discrimination, palmar abduction angle of the thumb, radial abduction angle of the thumb, and pinch force of the thumb were measured and compared before and at last follow-up, and the effectiveness was evaluated by Kapandji score and Disabilities of the Arm, Shoulder and Hand (DASH) score. The satisfaction of the operation was evaluated at last follow-up. Results All surgeries were successfully completed with a mean operation time of 54 minutes (range, 45-68 minutes). All patients were followed up 6-50 months, with an average of 15.3 months. There were no complications such as wound infection, scar pain of wrist, and tendon rupture of transposition, and there were 3 cases of mild limitation of finger extension in the donor site of index finger. At last follow-up, two-point discrimination, palmar abduction angle of the thumb, radial abduction angle of the thumb, Kapandji score, and DASH score were significantly better than those before operation (P<0.05), but there was no significant difference in thumb pinch force between pre- and post-operation (P>0.05). The evaluation of surgical satisfaction showed that 7 cases were very satisfied and 5 cases were satisfied. Conclusion The combination of endoscopic-assisted median nerve decompression and one-stage EIP tendon transfer effectively improves hand function and quality of life in patients with severe CTS by restoring thumb abduction and alleviating neurological symptoms.