[Objective] To investigate the clinical significance of percutaneous repair with Tightrope for distal tibiofibular syndesmosis instability diagnosed by ankle arthroscopy. [Methods] From November 2017 to March 2020, 41 patients received percutaneous Tightrope repair for distal tibiofibular syndesmosis instability that was found under ankle arthroscopy. The clinical and imaging documents were evalu- ated. [Results] All the 41 patients had operation completed with incisions healed in stage I, whereas without complication such as incision infection, neurovascular injury and lower limb deeper venous thrombosis. All patients were followed up for 24~52 months, with an average follow-up time of (35.4±7.7) months. During the follow-up, none of the 41 patients had complications such as incision infection, neurovas- cular injury, venous thrombosis of lower limbs and revision surgery. With time elapsed in points preoperatively, 6 months postoperatively, 12 months postoperatively and the latest follow- up, the VAS score significantly reduced [(4.4±2.8), (2.6±1.8), (1.8±1.6), (1.4±1.5), P＜ 0.001], while the AOFAS score [(60.9±28.6), (73.4±13.9), (82.2±14.0), (85.0±10.0), P＜0.001] and SF-36 score [(89.5±12.1), (98.8±12.9), (106.8±12.0), (112.2±13.4), P＜0.001] significantly increased, however, the ankle plantar flexion-dorsal extension range of motion (ROM) and pronation-supination ROM remained unchanged (P＞0.05). By the last follow-up, 39 patients regained the pre-injury exercise level, ac- counting for 95.1%. In terms of imaging, medial clear space (MCS), tibiofibular clear space (TFCS), tibiofibular overlap (TFO) was not signif- icantly changed (P＞0.05). [Conclusion] The ankle arthroscopic examination is efficient tool to find distal tibiofibular syndesmosis instabili- ty, while percutaneous Tightrope repair of distal tibiofibular syndesmosis instability does achieve satisfactory clinical outcomes in this study.