Abstract:[Objective] To compare the clinical efficacy of open reduction and internal fixation (ORIF) based on comprehensive classi-fication versus ORIF based on AO classification for pilon fractures, and to provide a reference for the surgical plan making. [Methods] Aretrospective study was conducted on 90 patients who received ORIF for pilon fractures from June 2017 to October 2019. According to thepreoperative doctor-patient communication, the patients were divided into two groups. Of them, 45 patients had ORIF performed based oncomprehensive classification (the comprehensive group), while other 45 patients had operation conducted based on the traditional AO classi-fication (the AO group). The documents of perioperative period, follow-up and images were compared between the two groups. [Results]The comprehensive group proved significantly superior to the AO group in terms of incision length [(13.2±1.5) cm vs (13.8±1.0) cm, P=0.018], intraoperative blood loss [(50.9±18.4) ml vs (63.8±17.6) ml, P＜0.001] and hospital stay [(13.4±3.6) days vs (16.2±5.6) days, P=0.006]. The average follow-up time was of (18.5±4.6) months, and the comprehensive group resumed full weight-bearing activity signifi-cantly earlier than the AO group [(84.4±6.1) days vs (87.3±7.4) days, P=0.046]. The ROM, VAS scores and AOFAS scores in both groupswere significantly improved over time (P＜0.05), which in the comprehensive group were significantly better than those in the AO group atall corresponding time points after surgery (P＜0.05). With respect of imaging, fracture reduction quality in the comprehensive group was sig-nificantly better than that in the AO group [excellent/good/poor, (17/22/6) vs (12/16/17), P=0.029]. Compared with those preoperatively, theheight, width, coronal angle and sagittal angle of ankle mortise in both groups were significantly improved at the last follow-up (P＜0.05). Atthe last follow-up, the comprehensive group proved significantly better than the AO group regarding to the height [(23.2±2.5) mm vs (24.3±2.5) mm, P=0.044], width [(39.9±2.3) mm vs (41.8±2.9) mm, P＜0.001], coronary angle [(6.4±1.1)° vs (6.9±1.0)°, P=0.044], sagittal angle ofthe ankle mortise [(13.0±1.3)° vs (13.7±1.6)°, P=0.030]. [Conclusion] The clinical consequence of ORIF based on comprehensive classifi-cation are significantly better than the ORIF based on AO classification, suggesting that comprehensive classification has important clinicalsignificance in guiding ORIF.