[Objective] To explore how to determine whether or not to fix the inferior tibiofibular syndesmosis during open reduction and internal fixation of ankle fractures. [Methods] A total of 26 patients, including 15 males and 11 females, aged 20~67 years with a mean of (47.26±16.03) years, underwent surgical treatment for ankle fractures from February 2016 to June 2020. Intraoperative external rotation test, or fluoroscopic assessment to observe whether the medial joint space was abnormally widened were conducted. If the result was nega- tive, the inferior tibiofibular syndesmosis was not fixed with screws, whereas if positive, the inferior tibiofibular syndesmosis was fixed with screws. [Results] All the 26 patients were successfully operated on without serious complications. According to the consequences of intraop- erative judgment, 12 patients underwent tibiofibular fixation, while the remaining 14 cases did not. The fixed group had significantly greater operative time and intraoperative fluoroscopy times than the non-fixed group (P<0.05) , but there were no significant differences in incision length, intraoperative blood loss and incision healing between the two groups (P>0.05) . All the 26 patients were followed up for more than 12 months. The fixed group resumed walking and full weight-bearing activity significantly later than that of the non-fixed group (P<0.05) . The AOFAS score and dorsal extension-plantar flexion range of motion (ROM) increased significantly in both groups over time postopera- tively (P<0.05) , however there were no significant differences in AOFAS score and ROM between the two groups at corresponding postoper- ative time points (P>0.05) . In terms of radiographic evaluation, the tibiofibular overlap (TFOL) significantly increased, while the tibiofibu- lar clear space (TFCS) significantly decreased postoperatively compared with those preoperatively in both groups (P<0.05) . At the matching time points, there was no significant difference in the above indexes between the two groups (P>0.05) . [Conclusion] Intraoperative external rotation test or fluoroscopic observation of abnormal widening of medial joint space do effectively determine whether to fix the inferior tibio- fibular syndesmosis during open reduction and internal fixation of ankle fractures.