To explore clinical effect of open reduction and internal fixation through a single lateral approach for Pilon fractures. From January 2016 to May 2017, 28 patients with Pilon fractures were treated with open reduction and internal fixation through a single lateral approach. Among them, including 17 males and 11 females, aged from 25 to 59 years old with an average of (39.2±12.2) years old; 13 patients on the left side and 15 patients on the right side; according to Rüedi-Allgöwer classificaton, 7 patients were typeⅠ, 11 patients were typeⅡ, 10 patients were type Ⅲ. All patients were performed external fixation or calcaneal traction within 24 h of emergency, and open reduction and internal fixation was performed after swelling of soft tissue. Healing of incision and fracture, postoperative complications were observed, and AOFAS score at 1 year after operation was used to evaluate ankle joint function. Twenty-eight patients were followed up from 12 to 25 months with an average of (16.4±7.2) months. Two patients occurred superficial wound infection caused delayed wound healing, 1 patient occurred partial skin necrosis and healed after wound dressing change. The healing time of incision ranged from 11 to 25 days with an average of (15.2±8.4) days. All patients got bone union and the time ranged from 12 to 18 weeks with an average of (15.2±3.4) weeks. Two patients suffered from ankle pain after walking postoperatively and X-ray showed traumatic arthritis, the pain got better with the treatment of non steroidal anti inflammatory drugs. No cases of deep infection, nonunion, delayed union, malunion, loosening of internal fixation occurred after operation. AOFAS score at 1 year after operation was 89.6±5.7, 14 patients got excellent results, 12 good, and 2 fair. The single lateral approach for surgical treatment of Pilon fractures could provide sufficient exposure, reduction and fixation with less soft tissue application and the clinical curative effect is satisfied. However, for Pilon fracture with varus deformity or comminuted fracture on the medial side of tibial, it is difficult to place the main plate on the medial side of tibial. Instead, anteromedial incision or extensive anterior incision is more suitable.