Abstract: OBJECTIVE To explore the impact of antibiotics on prevention of infection in orthopedics department patients during perioperative period. METHODS A total of 82 patients who received surgeries in orthopedics department in Ruian People’s Hospital from Jan 2016 to Jan 2019 were enrolled in the study and randomly divided into the control group and the study group, with 41 cases in each group. The control group was given conventional antibiotics during the perioperative period, and the study group was given interventional use of antibiotics. The use of antibiotics and costs of antibiotics were observed and compared between the two groups of patients, and the rationality of use of antibiotics was evaluated. RESULTS The length of hospital stay, surgical site infection and costs of treatments were significantly lower in the study group than in the control group（P＜0.05）. There was no significant difference in the body temperature between the two groups. The patients who were treated with single medication were dominant among the two groups of patients during the perioperative period; the patients who were treated with single medication were significantly more in the study group than in the control group, the patients who were treated with two-drug medication were significantly lower in the study group than in the control group（P＜0.05）. The rates of reasonable use of antibiotics such as selection of antibiotics, timing of antibiotics prophylaxis and time of postoperative use of antibiotics were higher in the study group than in the control group（P＜0.05）. There were no significant differences in the levels of serum inflammatory factors tumor necrosis factor-α（TNF-α）, interleukin（IL-6）, IL-8 and C-reactive protein（CRP） between the two groups before the treatment; the levels of serum inflammatory factors of the two groups were significantly reduced after the treatment（P＜0.05）. CONCLUSION The interventional use of antibiotics can achieve significantly effect on prevention of the infection during the perioperative period, it can reduce the incidence of surgical site infection, improve the rationality of use of antibiotics, shorten the length of hospital stay and reduce the cost of hospitalization.