For a study, researchers sought to assess the incidence of surgical site infections using preoperative surgical antibiotic prophylaxis (SAP) plus extra intraoperative redosing to single-dose preoperative surgical antibiotic prophylaxis (SSI). On June 25th, 2021, they searched MEDLINE (PubMed), Embase, CINAHL, and CENTRAL using PROSPERO registration CRD42021229035. Preoperative SAP with additional intraoperative redosing was compared to single-dose preoperative SAP (no redosing) on SSI incidence in patients undergoing surgery. Independently, 2 investigators appraised the data and extracted the summary data. Meta-analyses were broken down by study type. They estimated a pooled odds ratio with 95% CI using a generic inverse variance random-effects model (CIs). They included 9,470 patients in 8 cohort studies and 2 randomized controlled trials (RCTs). The pooled odds ratios for SSI in patients receiving intraoperative redosing versus those not receiving redosing were 0.47 (95% CI: 0.19–1.16, I2 = 36%) in RCTs and 0.55 (95% CI: 0.38–0.79, I2 = 56%) in observational cohorts. There was significant clinical heterogeneity in the antibiotics used and the redosing protocols. The GRADE assessment revealed that the overall certainty of the evidence was low. Based on trials with a wide range of antibiotic regimens and redosing protocols, intraoperative redosing of SAP may minimize SSI risk compared to a single dose preoperative SAP in any surgery.