Objective To investigate the efficacy of a procalcitonin (PCT)?guided antibiotic therapy strategy in patients after gastrointestinal perforation surgery. Methods A total of 118 patients who underwent gastrointestinal perforation surgery at our hospital from January 2021 to December 2025 were enrolled. According to the antibiotic therapy strategy, they were divided into a control group (n=59) and an observation group (n=59). The control group received conventional empirical antibiotic discontinuation, while the observation group additionally adopted serum PCT dynamic monitoring. The duration of antibiotic use, postoperative hospital stay, hospitalization costs, postoperative white blood cell (WBC) count and C-reactive protein (CRP) levels, postoperative infection-related complications, and the incidence of newly acquired multidrug-resistant organism (MDRO) infection during hospitalization were compared between the two groups. Results The duration of antibiotic use and postoperative hospital stay were shorter in the observation group than in the control group, and hospitalization costs were lower, with statistically significant differences (P<0.05). At 1 day postoperatively, there were no statistically significant differences in WBC and CRP levels between the two groups (P>0.05). At 5 days postoperatively, both WBC and CRP levels decreased compared with those at 1 day postoperatively in both groups (P<0.05), and the levels in the observation group were lower than those in the control group, with statistically significant differences (P<0.05). There was no statistically significant difference in the incidence of complications (including abdominal infection, wound infection, pulmonary infection, and urinary tract infection) between the two groups (P>0.05). The incidence of newly acquired MDRO infection during hospitalization was lower in the observation group than in the control group, with a statistically significant difference (P<0.05).SConclusion The PCT?guided antibiotic discontinuation strategy after gastrointestinal perforation surgery can effectively shorten the duration of antibiotic use and hospital stay, reduce hospitalization costs, alleviate inflammatory response, and does not increase the risk of infection?related complications, while also helping to reduce the incidence of MDRO infection.