Objectives: Meningoencephalitis (ME) is a well-recognized clinical entity with diverse infectious etiologies. Only a few studies in the Indian literature are available on this issue, especially in the adult population. The aim is to study the microbial etiology of ME presenting to a tertiary care center. Methods: A total of 97 cases labeled as ME were initially found on review of hospital records in a retrospective review over 5 years. Of these, only 62 were microbiologically confirmed and these were selected for this study. Results: Bacteria were the cause in 21(34%) cases. Pneumococcus was the predominant bacterial etiology, found in 17 cases (detected by PCR in 15 and by culture in 3 cases). Viruses were seen in 13 (21%) cases; Herpes simplex virus (HSV) was seen in 4 cases and enterovirus and varicella in 2 cases each (all were detected by PCR). We also had Arboviruses: Chikungunya (3 cases) and Dengue (2 cases) (serological diagnosis). TB was found in 15 (24%) cases (diagnosed by positive CSF Xpert Mtb in 11 cases and by AFB culture in 7 cases). Cryptococcus was seen in another 13 (21%) cases (detected by positive CSF CRAG in all cases and culture positivity in 7 cases). Conclusion: Pneumococcus and HSV are the commonest agents causing acute ME syndrome. Mycobacterium tuberculosis and Cryptococcus accounted for all cases of chronic ME. Multiplex PCR (in acute ME) and Xpert Mtb and cryptococcal antigen (in chronic ME) play an important role in the diagnosis of culture-negative ME.