The aim of this study was to determine the utility of prophylactic antibiotics before pyloromyotomy for the prevention of Surgical Site Infections (SSI) among children with Infantile Hypertrophic Pyloric Stenosis (IHPS). A systematic search of PubMed, Scopus, Embase, and Web of Science databases was performed to identify papers published till 30th July 2024. The main outcome of interest was the incidence of SSIs. The relative risk (RR) with 95% confidence interval (CI) was calculated using a random effects model. The I2 statistic was used to calculate the heterogeneity. The Newcastle-Ottawa-Scale (NOS) was used to assess the methodological quality of the included studies. Five studies, published between 1999 and 2024, were included in this systematic review and meta-analysis. The risk of developing SSI among those treated was RR = 0.97, 95% CI 0.53 to 1.78, with I2 = 0%, indicating no incremental benefit of administration of prophylactic antibiotics. A sensitivity analysis was performed by excluding the database studies. Results from this analysis (RR = 0.79, 95% CI 0.29 to 2.20, I2 = 0%) demonstrated that no significant difference was observed after excluding studies with large sample sizes. All included studies were of good methodological quality as assessed with the NOS. The findings of this review demonstrate no incremental benefit of the administration of prophylactic antibiotics before pyloromyotomy in preventing SSIs in children with IHPS. However, randomized, double-blinded, placebo-controlled trials need to be conducted in the future before any definite conclusions are drawn in this regard.