Introduction Encephalopathy is a term that means brain disease, damage, or malfunction. Encephalopathy can present a very broad spectrum of symptoms that range from mild, such as some memory loss or subtle personality changes, to severe, such as dementia, seizures, coma or death. In general, encephalopathy is manifested by an altered mental state that is sometimes accompanied by physical manifestations (for example, poor coordination of limb movements). The diagnosis of encephalopathy is usually made with clinical tests done during the physical examination (mental status tests, memory tests, and coordination tests) that document an altered mental state. In most cases, findings on clinical tests either diagnose or presumptively diagnose encephalopathy. Usually, the diagnosis is achieved when the altered mental state accompanies another primary diagnosis such as chronic liver disease, kidney failure, anoxia, or many other diagnoses. Materials & Methods This is a Prospective observational study conducted in the Inpatient Department of Paediatric, Tertiary Care Teaching Hospital. MRI/CT brain will be performed according to the clinical requirement and patient condition at initial admission. If there is clear diagnostic information on initial imaging no further neuroimaging will be performed on these children unless a prognostic imaging is deemed necessary by treating neurologist. Delayed imaging will be done when the initial neuroimaging is normal/nondiagnostic and child continues to have neurological symptoms and signs without obvious diagnoses from clinical, blood, CSF investigations. Also, when there are new onset neurological symptoms/ progressive worsening of neurological status after initial neuroimaging. Result In 21.95% of cases, second scan was done on 4th day of illness followed by 12.19% of cases on 3rd day. Second scan was done from 4th-10th day of illness in 56.09% followed by 1st-3rd day and 11th -20th day in 19.51% and 17.07% respectively. Second scan was diagnostic in 80.48% of cases and nonspecific findings in 4.87% of cases and was normal in only 4.87% of cases. Reason for second neuroimaging was Clinical Worsening in 41.46% and No Clinical Improvement in 31.7% of cases. Second neuroimaging was Diagnostic in 9.75% of cases. Delayed neuroimaging and Both Neuroimagings were equally helpful in majority of cases (78.04%) and no neuroimaging was helpful in 17.07% of cases. First neuroimaging was diagnostic in 46.34% of cases and not diagnostic in 56.68%of cases. Second neuroimaging was diagnostic in 60.97% of cases and nondiagnostic in 34.14% of cases. Conclusions The present study demonstrates that there is a subjective component to scan interpretation, which can have important implications for the clinical management of acute encephalopathy cases. The agreement between raters was good for CT but only moderate for MRI. Agreement varied with diagnosis; for blinded reading radiologists were good at diagnosing acute encephalopathy; however, agreement was worse for ADEM and other alternative aetiologies. The study showed that imaging data are affected by imaging timing and technique, and there was poor agreement on some regional abnormalities.