Objective To explore the effectiveness of interlocking intramedullary nail fixation system for Sanders type Ⅱ and Ⅲ calcaneal fractures by comparing with open surgery. Methods Forty patients (40 feet) with Sanders type Ⅱ and Ⅲ calcaneal fractures, who were admitted between May 2020 and December 2022 and met the selection criteria, were included in the study. They were randomly allocated into control group and minimally invasive group using a random number table method, with 20 cases in each group. The patients were treated with the interlocking intramedullary nail fixation system in the minimally invasive group and with steel plate internal fixation via a lateral L-shaped incision in the control group. There was no significant difference between the two groups (P>0.05) in terms of gender, age, fracture classification and side, cause of injury, time from injury to admission, and preoperative width, length, height, Böhler angle, and Gissane angle of the calcaneus. The operation time, intraoperative blood loss, incision length, hospital stay, fracture healing time, incidence of complications, as well as pre- and post-operative imaging indicators (Böhler angle, Gissane angle, width, height, and length of the calcaneus) and American Orthopaedic Foot and Ankle Society (AOFAS) score of foot were recorded and compared between the two groups. Results The incision length, operation time, and hospital stay of the minimally invasive group were significantly shorter than those of the control group, and the intraoperative blood loss significantly reduced (P<0.05). All patients of the two groups were followed up, with the follow-up time of 8-12 months (mean, 10.2 months) in the minimally invasive group and 8-12 months (mean, 10.4 months) in the control group. No complication occurred in the minimally invasive group after operation. One case of incision epidermal necrosis and 1 case of traumatic arthritis occurred in the control group after operation. However, there was no significant difference in the incidence of complications between the two groups (P>0.05). At last follow-up, the AOFAS score was significantly higher in the minimally invasive group than in the control group (P<0.05). Imaging examination showed that the calcaneal fractures of the two groups healed, and there was no significant difference in healing time between the two groups (P>0.05). Compared with preoperative conditions, the Böhler angle and Gissane angle of the calcaneus in the two groups significantly increased, the width narrowed, and the height and length increased at 3 days after operation and the last follow-up, with significant differences (P<0.05). There was no significant difference between 3 days after operation and last follow-up (P>0.05). There was no significant difference between the two groups at each time point (P>0.05). ConclusionThe interlocking intramedullary nail fixation system in treatment of Sanders type Ⅱ and Ⅲ calcaneal fractures has the advantages of minimal trauma, shortened hospital stay, reliable fracture reduction and fixation, and satisfactory foot function recovery.