Objective: To investigate the application of the axillary central venous catheterization (CVC) based on Nickalls' landmarks in treating adult multiple injury patients. Methods: A retrospective case control study was conducted to analyze the clinical data of 83 adult multiple injury patients treated in Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from August 2017 to August 2018. There were 48 males and 35 females, aged 21-84 years [(56.5±14.3)years]. The body mass index ranged from 19.8 to 43.1 kg/m² [(27.6±6.5)kg/m²]. There were 26 patients with mainly craniocerebral injury, 15 with mainly thoracic injury, 28 with mainly abdominal injury, eight with mainly spinal injury and six with mainly pelvic fracture. The injury severity score (ISS) ranged from 24 to 66 points [(41.8±18.1)points]. All the patients received the axillary CVC based on Nickalls' landmarks. The left axillary vein was used as the puncture vein in 16 patients (left group), and the right axillary vein was used as the puncture vein in 67 patients (right group). A total of 36 patients were combined with the clavicle and/or 1-3 rib fractures at the same side as the puncture site (adjacent fracture group), while 47 patients were not combined with the clavicle and/or 1-3 rib fractures at the same side as the puncture site (non-adjacent fracture group). The success rate of catheterization, pneumothorax, hematoma or artery injury, catheter ectopia, catheter-related infection and catheter-related thrombosis were recorded. Results: A total of 80 patients were successfully intubated, with a success rate of 96%. Subgroup analysis showed that the success rate of right group was [97% (65/67)], slightly higher than that of the left group [94%(15/16)] , but the difference was not statistically significant (P>0.05). And the success rate of adjacent fracture group [94%(34/36)] was similar to that of non-adjacent fracture group [98%(46/47)], and the difference was not statistically significant (P>0.05). Complication incidences were as follows: hematoma or arterial injury [5%(4/83)], pneumothorax 2%(2/83), catheter-related thrombosis [12%(10/83)], and catheter ectopia [1%(1/83)]. No catheter-related infection was observed. Subgroup analysis showed that the incidence of various complications was similar between the left group and the right group (hematoma or arterial injury: 6% vs. 4%, pneumothorax: 0% vs. 3%; catheter ectopic: 0% vs. 1%; catheter-related thrombosis: 13% vs. 12%), and the difference was not statistically significant (P>0.05). The incidence of various complications was also similar between the adjacent fracture group and the non-adjacent fracture group (hematoma or arterial injury: 3% vs. 6%; pneumothorax: 3% vs. 2%; catheter ectopic: 0% vs. 2%; catheter-related thrombosis: 17% vs. 9%), and the difference was not statistically significant (P>0.05). Conclusions Axillary CVC based on Nickalls' landmark has a relatively high catheterization success rate and low complication incidence in adult multiple trauma patients. It is applicable to both left and right sides of axillary vein and suitable for patients with adjacent fracture. However, there still exists a high risk of catheter-related thrombosis, requiring enhanced anticoagulation and regular monitoring of thrombosis during catheterization.