AbstractBackgroundAppropriate antibiotic prophylaxis is essential for preventing surgical site infections (SSI); however, the clinical benefit of intraoperative redosing remains unclear and controversial owing to insufficient reliable evidence. Therefore, we performed a systematic review and meta‐analysis to assess the effectiveness of prophylactic antibiotic redosing in lengthy surgical procedures.MethodsWe systematically searched the PubMed, Cochrane Library, Web of Science, and Ichushi‐Web databases for articles published until 31 December, 2023. We compared the incidence of SSI between patients receiving and not receiving intraoperative redosing of antibiotics in surgeries lasting ≥3 h. Subgroup analyses were conducted across study characteristics. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the Mantel–Haenszel random effects model. The risk of bias was assessed using the ROBINS‐I.ResultsOverall, seven observational studies involving 4,671 patients were included. Intraoperative antibiotic redosing significantly reduced the risk of SSI compared with non‐redosing (OR = 0.65, 95% CI = 0.45–0.94, p = 0.02). Subgroup analyses showed that intraoperative redosing decreased SSI risk in studies with a minimum 4‐h operative time, no postoperative antibiotic continuation, and a moderate risk of bias. However, the statistical heterogeneity of the analyses was high among the studies.ConclusionsIntraoperative redosing with prophylactic antibiotics during lengthy surgeries may be associated with a lower risk of SSI than non‐redosing. Therefore, we recommend intraoperative redosing for surgeries lasting beyond 3–4 h to reduce the risk of infection. Further research is required to clarify the optimal redosing interval, which should be prioritized in future studies.