The present study investigated the effects of vacuum sealing drainage (VSD) to improve the therapeutic efficacy in patients with orthopedic trauma (OT) and reduce post-operative infection and lower-limb deep venous thrombosis (DVT) through a retrospective analysis. A total of 76 patients with OT treated at our hospital were selected for observation. The patients were divided into the control group (CG; n=37) and the experimental group (EG; n=39) according to the treatment administered. For patients in the CG, routine dressing changes were applied. Patients in the EG underwent VSD treatment. The dressing change frequency, time between the first and second operation, hospital stay, treatment efficacy, wound healing time, interleukin-6 (IL-6) serum level, tumor necrosis factor-α (TNF-α) serum level, incidence of post-operative infection and incidence of lower-limb DVT were compared between the two groups. The dressing change frequency in the EG was less than that in the CG. The time between the first and second operation and hospital stay were shorter in the EG than in the CG (P<0.05). The total effective rate in the EG was 97.44%, which was higher than that in the CG (78.38%; P<0.05). The wound healing time in the EG was 1.72±0.73 weeks and shorter than that in the CG (2.23±0.85 weeks; P<0.05). With the progression of treatment, the serum IL-6 and TNF-α levels decreased in the two groups, but the levels in the EG were lower than those in the CG (P<0.05). The incidence of post-operative infection and lower-limb venous thrombosis in the EG were 7.69 and 0.00%, respectively, and lower than those in the CG (27.03 and 13.01%, respectively; P<0.05). In the treatment of OT, VSD may reduce the dressing change frequency, shorten the operation time and hospital stay, accelerate wound healing and reduce post-operative infection and lower-limb DVT. Thus, the VSD treatment method is worthy of promotion and implementation in clinic.