Context: Japanese encephalitis (JE), an acute mosquito-borne viral disease, is one of the leading causes of viral encephalitis in the South-East Asian region. JE is endemic in Assam. The morbidity and mortality due to JE is significant with outbreaks every year during the monsoons. Aims: The aim was to study the clinicopathological profile of JE; to examine their role in predicting disease outcome; and to document the increase in the incidence of JE among the adult population in this region. Materials and Methods: Clinically suspected acute encephalitis syndrome (AES) cases admitted in Assam Medical College and Hospital during the period of May 2011 to April 2012 were tested by JE virus specific Immunoglobulin M capture ELISA. Statistical Analysis Used: Data analysis was performed using SPSS version 16.0. Results: Out of 424 AES cases, 194 were JE positive. The occurrence of JE in adults was higher (P < 0.001) than the pediatric age group. The study recorded a high rate of renal dysfunction in JE cases. A single case of JE induced abortion and two cases of JE-neurocysticercosis co-infections were documented. Regression analysis revealed that adult population, unconsciousness, paresis and elevated cerebrospinal fluid protein level were associated with a worse prognosis in JE cases. Mortality in JE positive cases was higher than the JE negative cases (P = 0.001). Conclusion: The study attempts to highlight the role played by a combination of clinical and laboratory parameters in assessing the severity and outcome in JE and may help in directing the limited medical resources toward those that need it the most.