Background: In the skeletally mature anterior cruciate ligament (ACL) reconstruction population, patients aged <25 years are at significantly increased risk of graft failure and injury to the contralateral ACL. Skeletal immaturity often affects graft selection and reconstruction technique. Purpose: To examine the incidence of ipsilateral graft failure and contralateral ACL injury in the skeletally immature patient population. Study Design: Systematic review and meta-analysis. Methods: Using the PRISMA (Preferred Reporting Items for Systematic Meta-Analyses) guidelines, we reviewed all literature that involved ACL reconstruction performed on skeletally immature patients between May 1976 and May 2019. Patient demographics, surgical technique, and the prevalence of ipsilateral graft failure or subsequent contralateral ACL injury were recorded. Ipsilateral, contralateral, and secondary ACL injuries were then compared between sexes via chi-square tests. Results: A total of 24 articles (1254 children; 1258 knees) met inclusion criteria for analysis. Ipsilateral graft failures occurred in 105 of 1258 patients (8.3%), and there were no statistically significant sex differences in the prevalence of graft failures (female, 9.7%; male patients, 7.1%; P = .14). The prevalence of contralateral ACL injury was significantly greater in female (29/129; 22.5%) than male (18/206; 8.7%; P = .0004) patients in the 9 studies that reported contralateral injury. Skeletally immature female patients were at significantly increased risk of contralateral ACL injury (odds ratio = 3.0; P = .0006) when compared with their male counterparts. Conclusion: In the literature to date, 1 in 3 female skeletally immature patients experienced an ipsilateral graft failure or contralateral ACL injury. Regardless of sex, the 24% prevalence of secondary injury after pediatric ACL reconstruction is almost identical to previously published secondary injury rates in skeletally mature patients <25 years old. As such, skeletal maturity alone does not seem to be a determinant of secondary injury; however, there is a clear need to improve postoperative rehabilitation, activity progression, and return-to-play testing to allow a safe return to sports that protects the long-term health of the reconstructed and contralateral limbs, especially for female patients.