Objective To understand the preventive effect of pneumatic compression therapy on deep vein thrombosis (DVT) in lower limbs of patients with spinal cord injury. Methods Patients with spinal cord injury who transferred from Orthopedics Department to Rehabilitation Department undergoing rehabilitation in the First Affiliated Hospital of University of Science and Technology of China and discharged from April 2017 to December 2020 were retrospectively included. According to the contents of the medical order of the case data, the patients were divided into treatment group and control group. The intervention method of the treatment group was pneumatic compression therapy and conventional rehabilitation treatment, and the control group was conventional rehabilitation treatment. Multivariate logistic regression was used for statistical analysis to explore the association of pneumatic compression therapy and the risk of DVT in patients with spinal cord injury. Results Finally, 153 patients were enrolled, including 71 cases in the treatment group and 82 cases in the control group. After rehabilitation therapy, DVT occurred in 10 cases (14.1%) in the treatment group and 21 cases (25.6%) in the control group. There was no significant difference in incidence of DVT between the two groups (χ2=3.129, P=0.077). After six months of follow-up, DVT occurred in 11 cases (15.5%) in the treatment group and 12 cases (14.6%) in the control group. There was no significant difference in incidence of DVT between the two groups (χ2=0.022, P=0.822). D-dimer [odds ratio (OR) =1.104, 95% confidence interval (CI) (1.036, 1.175), P=0.002] and age [OR=1.081, 95%CI (1.040, 1.124), P<0.001] were independent risk factors for the risk of DVT after treatment. Pneumatic compression therapy was a protective factor for the risk of DVT [OR=0.210, 95%CI (0.075, 0.591), P=0.003]. Age [OR=1.057, 95%CI (1.008, 1.108), P=0.023] was an independent risk factor for the risk of DVT after six months. The effect of pneumatic compression therapy was not statistically significant (P=0.393). Conclusions After spinal cord injury, it is necessary to strengthen the management of high serum D-dimer state, especially the risk of DVT in elderly patients. Pneumatic compression therapy could be used as a treatment measure to reduce risk of DVT in patients with spinal cord injury during hospitalization, however, the preventive effect after half a year needs to be further studied.