Abstract Introduction Congenital anomalies are one of the leading causes of mortality in neonatal period. The burden of genetic disease is high in neonates with congenital anomalies. Chromosomal microarray analysis (CMA) is the “first-tier” cytogenetic diagnostic test for individuals with multiple congenital anomalies. The aim of this study is to assess the diagnostic yield and clinical management impact of CMA in a large neonatal cohort over a 10-year period at a single medical center. Methods This is a retrospective study of a cohort of neonates tested by CMA at UVA Cytogenetics Laboratory between the years of 2013-2022. All individuals had either an isolated (major) congenital anomaly (CA) or multiple congenital malformations (MCA). We evaluated the diagnostic yield of the CMA in this neonate cohort and the frequency of positive CMA findings for specific phenotypes, as well as impact of CMA findings in the clinical management of patients. Results Of the 965 patients analyzed, 656 (68%) had normal results, 166 (17%) patients only had variants of uncertain significance (VUS), 128 (13%) patients had pathogenic alterations (thus confirmed genetic diagnosis), and 15 (2%) patients only had absence of heterozygosity (AOH) regions meeting our reporting criteria. Further details on presence of specific CNVs in the cohort and, positivity per presence/absence of multiple and specific anomalies is still ongoing and will be given in the presentation. For patients received a genetic diagnosis through CMA analysis, genetic findings were considered beneficial for clinical management, and a direct change to medical management occurred. Conclusion s: In this study, we found that the overall diagnostic yield for CMA in this neonate cohort is at approximately 13%. The confirmed genetic diagnosis affected the clinical management/treatment plan of this subset of neonatal patients. While first-tier testing for MCA and other indications is increasingly moving to ES/GS approaches, CMA continues to offer diagnostic and actionable genetic information in a timely matter. Overall, the implementation of CMA to a neonatal cohort at our center has increased the proportion of patients receiving a confirmed genetic diagnosis and affected the management/treatment plan of a subset of neonatal patients.