Abstract:[Objective] To compare the clinical outcomes of arthroscopic reduction and percutaneous cannulated screw fixation versus open reduction and internal fixation (ORIF) with plate through tarsal sinus approach for calcaneal fractures. [Methods] A total of 102 patients with calcaneal fracture admitted to our hospital from January 2019 to October 2022 were included into this study and randomly divided into two groups by drawing lots. Among them, 51 patients were treated with arthroscopic reduction and percutaneous screw fixation (the ARPSF group), while other 51 patients underwent ORIF through tarsal sinus approach (the ORIF group). The data of perioperative period, follow-up and auxiliary examination were compared between the two groups. [Results] The ARPSF group consumed significantly longer operation time than the ORIF group [(48.5±5.2) min vs (45.7±4.6) min, P=0.007], but the former proved significantly superior to the latter in terms of incision length [(1.6±0.5) cm vs (4.0±1.0) cm, P＜0.001], intraoperative blood loss [(10.5±3.4) ml vs (30.3±9.2) ml, P＜0.001] and length of stay [(5.7±1.8) days vs (7.4±2.0) days, P＜0.001]. All patients in both groups were followed up for (18.2±2.6) months in a mean, and the ARPSF group resumed ambulation [(38.5±4.6) days vs (42.0±5.4) days, P＜0.001] and full weight-bearing activity [(65.8±6.7) days vs (70.5±8.0) days, P=0.003] significantly earlier than the ORIF group. As time went on, the dorsal-plantar ankle range of motion (ROM), inversion-eversion ROM and AOFAS score were significantly increased (P＜0.05), while the VAS scores were significantly decreased in both groups (P＜0.05), which in the ARPSF group at 3 months after operation were significantly better than those in the ORIF group (P＜0.05). As for auxiliary examination, the levels of serum BMP-2 and IGF-1 were significantly increased (P＜0.05), while the levels of sVCAM-1 and HMGB1 were significantly decreased in both groups (P＜0.05), which in the ARPSF group proved significantly better than those in the ORIF group 3 months after surgery (P＜0.05). In addition, the Bohler and Gissane angles, as well as joint surface collapse were significantly im-proved in both groups at the last follow-up compared with those preoperatively (P＜0.05), whereas which were not significantly different between the two groups at any matching time points (P＞0.05). [Conclusion] The arthroscopic reduction and percutaneous cannulated screw fixation of calcaneal fracture does significantly reduce surgical trauma, shorten hospital stay, and facilitates the process of functional rehabilitation.