Background: The echocardiogram permits early accurate anatomical diagnosis either to reassure parents that the heart was normal, or to detect a heart disease and explain the nature of the abnormality and make an early referral for definitive treatment. Aim: Assessment of neonatal cardiac murmurs clinically and by echocardiogram at birth and at 6 weeks of age. Materials and Methods: A prospective longitudinal study was conducted on neonates for a period of one year at Government Mohan Kumaramangalam Medical College Hospital, Salem. Cardiac murmur was graded between 1 and 6 based on the intensity of the murmur. All neonates underwent an echocardiographic examination by Cardiologists at 1 st week and later at 6 weeks. Results: The incidence of murmur in the first week of life was 23/1000 live births and the incidence of congenital heart disease was 12.6/1000 live births and at 6 weeks it was 6.6/1000 live births. The most common congenital heart disease during the 1 st week examination was found to be VSD, followed by ASD and PDA. Identifying a pathological murmur and its association with structural congenital heart disease was found to be statistically significant (p<.05), whereas identifying an innocent murmur and its association with a normal heart did not show a statistical significance and so it infers that all the innocent murmurs has to be followed up with a echocardiogram to rule out structural heart disease in the neonates. Conclusion: It is important to evaluate all neonatal cardiac murmurs with echocardiogram before they become symptomatic.