Objective To investigate the clinical efficacy between suture button plate and cortical screw in the treatment of distal tibiofibular syndesmosis seperation. Methods The clinical data and follow-up data 1 week and 2, 4, 6 weeks and 3, 6, 12 months after operation of patients with distal tibiofibular syndesmosis seperation combined with or without ankle fracture who were admitted to hospital from March 2011 to May 2014 were retrospectively collected. According to the fixation ways of distal tibiofibular syndesmosis, the patients were divided into the suture button plate group and the cortical screw group. The operation time, amount of blood loss, combined ankle fracture healing time, American Orthopaedic Foot and Ankle Society (AOFAS) scores at the last follow-up and complications were compared between the two groups. Results A total of 52 patients were enrolled, including 28 cases of suture button plate group and 24 cases of cortical screw group. There were no significant difference in operation time or amount of blood loss between the two groups (P>0.05). All patients were followed up for 12–30 months averaged 14.5 months. All incisions healed by the first intention. The combined ankle fracture healing time in the suture button plate group was (11.2±2.0) weeks, while that was (11.0±2.1) weeks in the cortical screw group, with no significant difference between the two groups (P>0.05). In the suture button plate group, there was no loosening or rupture of internal fixation, while distal tibiofibular syndesmosis seperation was found again in one case 3 weeks after operation, and cured by reoperation at last. In the cortical screw group, rupture of screws was found in 2 cases, which occurred 9 and 11 weeks after operation respectively, and the broken screws were taken out when the fractures were healed and the internal fixation was removed; distal fibiofibular syndesmosis seperation was found again in one case 6 weeks after operation, and no treatment was given due to old age and low demand. At the last follow-up, the AOFAS score in the suture button plate group was 84.6±10.2, while the score in the cortical screw group was 83.7±12.5, with no significant difference between the two groups (P>0.05). Conclusions Suture button plate and cortical screw can effectively treat distal fibiofibular syndesmosis separation. The risk of suture button plate loosening or rupture is poor. Suture button plate fixation can meet the need of early functional exercises, and avoid the routine removal by reoperation.