A malformation is a structural defect arising from a localized error in morphogenesis that results in the abnormal formation of a tissue or organ. Early intrauterine period (between 3rd to 8th weeks of gestation) is the vital period of life for the normal development of organs. Any insult within this period may result in congenital abnormalities. Congenital anomalies account for 8–15% of perinatal deaths and 4-8% of neonatal deaths in India. Aims and Objectives-To study the morbidity and mortality profile of neonates born with major congenital anomalies in Southern Rajasthan. Materials and Methods- The present study was a descriptive observational study conducted between January 2021 to December 2021 at NICU of teaching hospital of Southern Rajasthan including babies admitted for CMF during neonatal period. Results- Incidence of Major CMF in our setting was 0.63% (86 of 13448 inborn live births). Out of 253 neonates admitted with CMF, most common anomalies were of G.I. system (60%) followed by CNS (21.7%) and multisystem involvement (7%). Tracheoesophageal fistula, (23.7%) Anorectal malformations (19.7%) and meningomyelocele (15.8%) constituted major chunk of the malformation. Out of 253 babies 71.5% were operated. Among neonates operated 51.5% babies developed septicemia,9%anaemia and 3% wound dehiscence postoperatively. Mean duration of hospital stay was 7 days with 40% babies being hospitalised for >10 days. Overall case fatality rate of CMF was 19.76%. Mortality rate of TEF and ARM was 18.6% and 15% respectively. Conclusion-Mortality rate in CMF remains very high despite the availability of surgical intervention. Owing to its high incidence and high mortality Major congenital malformations take a heavy toll on health care system. Timely surgical intervention is of prime importance for the prognosis.