Objective: To investigate the effect of application of bundle strategy on the prevention of surgical site infection in patients undergoing orthopaedic implantation. Methods: A total of 1 800 patients with orthopaedic implantation who were admitted to Wuxi Ninth People’s Hospital from March 2020 to March 2022 were selected and divided into 2 groups by random number table method, with 900 cases in each group. The control group implemented the conventional infection control program, and the experimental group implemented the bundle strategy on this basis. The incidence of surgical site infection, perioperative indicators, and postoperative serum inflammatory factor levels were compared between the 2 groups. Results: The incidence of surgical site infection in the experimental group was 1.44% (13/900), and the incidence of surgical site infection in the control group was 2.78% (25/900), the difference was statistically significant (P<0.05). The amount of intraoperative blood loss and hospital stay in the experimental group were less than those in the control group. The postoperative hemoglobin was higher than that of the control group (P<0.05); the levels of C-reaction protein (CRP), interleukin (IL)-6, IL-10, and tumor necrosis factor-α (TNF-α) in the experimental group on the 2nd postoperative day were lower than those in the control group, and the levels of WBC, CRP, procalcitonin (PCT), IL-6, IL-10, IL-1β, and TNF-α in the experimental group on the 5th postoperative day were lower than those in the control group (all P<0.05). A total of 38 of the 1 800 patients developed surgical site infection, and 43 pathogenic bacteria were isolated and cultured, including 19 Gram-positive bacteria, 23 Gram-negative bacteria, and 1 fungus. The Gram-positive bacteria susceptibility test showed that Staphylococcus aureus and Staphylococcus epidermidis had the highest resistance rate to ampicillin and cefazolin, and the highest sensitivity rate to vancomycin, reaching 100%. The drug susceptibility test of Gram-negative bacteria showed that the resistance rates of Escherichia coli to ciprofloxacin and levofloxacin were high; the sensitivity rate to polymyxin was the highest, reaching 100%; Pseudomonas aeruginosa was resistant to polymyxa. The highest sensitivity rate was 100%. Conclusion: The application of bundle strategy in patients with orthopaedic implantation can effectively reduce the level of serum inflammatory factors and reduce the occurrence of surgical site infection, thereby improving the prognosis.