Introduction: While continuous antibiotic prophylaxis (CAP) is currently recommended to prevent urinary tract infections (UTIs) in infants with prenatal hydronephrosis (HN), this recommendation is not evidence-based. The objective of this study was to systematically determine whether CAP reduces UTIs in the HN population.Methods: Applicable trials were identified through an electronic search of MEDLINE (1946‒2015), EMBASE (1980‒2016), CINAHL (1982‒2016), and CENTRAL (1993‒2016) and through a hand search of American Urological Association (AUA) (2012‒2015) and European Society for Pediatric Urology (ESPU) (2012‒2015) abstracts, as well as reference lists of included trials. The search strategy was not limited by language or year of publication. Eligible studies compared CAP to no CAP in patients with antenatal HN, <2 years of age, and reported development of UTI and HN grades. Two independent reviewers performed title and abstract screening, full-text review, and quality appraisal.Results: Of 1518 citations screened, 11 were included, contributing 3909 patients for final analysis. Of these, four (36%) were considered high-quality when assessed by the Newcastle Ottawa Scale. Meta-analysis of the non-randomized trials (n=10) provided similar pooled UTI rates, regardless of CAP use: 9.9% (95% confidence interval [CI] 8.4‒11.4%) for CAP and 7.5% (95% CI 6.4‒8.6%)for no CAP.Conclusions: This systematic review and meta-analysis suggests there may be value in providing CAP to infants with high-grade HN; however, due to the very low-quality data from non-randomized studies, important clinical variables, such as circumcision status, were unable to be assessed.