Postoperative infections in pediatric spinal surgery commonly occur and necessitate reoperation(s). However, pediatric-specific infection prophylaxis guidelines are not available. This network meta-analysis compares perioperative prophylaxis methods including Betadine irrigation, saline irrigation, intrawound vancomycin powder, combination therapy (Betadine, vancomycin, gentamicin, and cefuroxime), Betadine irrigation plus vancomycin powder, and no intervention to determine the most efficacious prevention method. A systematic review was performed by searching the PubMed, EBSCO, Scopus, and Web of Science databases for peer-reviewed articles published prior to February 2022 comparing two or more infection prophylaxis methods in patients younger than 22 years of age. Data were extracted for treatment modalities, patient demographics, and patient outcomes such as total number of infections, surgical site infections, deep infections, intraoperative blood loss, operative time, follow-up time, and postoperative complications. Quality and risk of bias was assessed using National Institutes of Health tools. A network meta-analysis was performed with reduction of infections as the primary outcome. Overall, 10 studies consisting of 5164 procedures were included. There was no significant difference between prophylactic treatment options in reduction of infection. However, three treatment options showed significant reduction in total infection compared with no prophylactic treatment: Betadine plus vancomycin (OR 0.22, 95% CI 0.09-0.54), vancomycin (OR 3.26, 95% CI 1.96-5.44), and a combination therapy (Betadine, vancomycin, gentamicin, and cefuroxime) (OR 0.24, 95% CI 0.07-0.75). P-Score hierarchical ranking estimated Betadine plus vancomycin to be the superior treatment to prevent total infections, deep infections, and surgical site infections (P-score 0.7876, 0.7175, and 0.7291, respectively). No prophylaxis treatment-related complications were reported. The results of this network meta-analysis show the strongest support for Betadine plus vancomycin as a method to reduce infections following pediatric spinal surgery. There was heterogeneity among studies and inconsistent outcome reporting; however, three effective treatment options are identified.