Abstract:[Objective] To compare the clinical efficacy of intramedullary nailing (IN) versus plate combined with TightRope for middle and distal fibular fractures complicated with inferior tibiofibular separation. [Methods] A retrospective study was done on 40 patients who had middle and distal fibular fracture complicated with inferior tibiofibularseparation treated by internal fixation and tibiofibular TightRope fixation in our hospital from January 2020 to December 2022. According to doctor-patient communication, 20 patients were fixed with the INl, while the other 20 patients were fixed with the plate. The documents of perioperative period, follow-up and imaging were compared between the two groups. [Results] All patients in both groups had operation performed successfully. The IN group proved significantly superior to the plate group in terms of operation time [(117.1±24.5) min vs (147.2±26.6) min, P<0.001], incision length [(4.1±1.7) cm vs (6.9±3.5) cm, P=0.003], intraoperative blood loss [(175.8±26.4) mL vs (199.4±22.5) mL, P=0.004], intraoperative fluoroscopy times [(5.7±1.2) times vs 7.1±1.5) times, P=0.002], incision healing grade [A/B/C, (20/0/0) vs (16/4/0), P=0.035], ambulation time [(3.5±1.2) days vs (5.1±1.7) days, P<0.001] and hospital stay [(9.6±4.8) days vs (14.6±5.3) days, P=0.003]. The average follow-up time was of (13.0±0.6) months, and the IN group resumed full weight-bearing activity significantly earlier than the plate group [(68.2±5.1) days vs (75.8±8.8) days, P=0.003]. The IN group was significantly better than the plate group in terms of the VAS score [(3.4±0.9) vs (4.5±1.0), P<0.001; (0.5±0.3) vs (1.0±0.6), P= 0.002], AOFAS score [(76.5±5.3) vs (70.1±6.1), P<0.001; (92.8±3.1) vs (89.3±4.2), P=0.005] 1 month after surgery and at the last follow-up, additionally, the plantar flexion-dorsal extension ROM [(32.9±5.6)° vs (27.8±4.9)°, P=0.004] 1 month postoperatively. Regarding imaging, the IN had poorer fracture reduction quality than the plate group (P<0.05), but the IN group got fracture healing significantly better than the plate group (P<0.05). However, the IN group proved significantly superior to the plate group in terms of the medial clear space (MCS) and tib-iofibular clear space (TFCS) at the latest follow-up (P<0.05). [Conclusion] Intramedullary nailing combined with TightRope fixation might be the better choice for the treatment of the middle and distal fibula fractures complicated with inferior tibiofibular separation.