Introduction: Early identification of etiology is very important for initiating appropriate therapy promptly in patients with meningoencephalitis (ME). BioFire FilmArray® meningitis/encephalitis (FA-ME) panel is a fully automated multiplex polymerase chain reaction (PCR) that detects 14 pathogens simultaneously in an hour. There is a dearth of studies highlighting its usefulness in ME syndrome in Indian patients. Materials and methods: We performed a retrospective analysis of patients, admitted to the Kerala Institute of Medical Sciences Hospital, Thiruvananthapuram, Kerala, South India, with meningitis/encephalitis syndrome who underwent the multiplex PCR test on cerebrospinal fluid (CSF) over a period of 2 years from 2016 to 2018. Patients presenting with clinical diagnosis of acute meningitis, encephalitis, or ME who underwent CSF FA-ME panel were studied. The performance of the FA-ME panel was compared to CSF bacterial culture. Results: Two-hundred and fifty-nine patients between December 2016 and December 2018 underwent the FA-ME test in CSF. FA-ME test detected pathogens in 61 (23.6%) out of 259 patients with ME syndrome. Among the pathogens detected by FA-ME panel, enterovirus was the commonest accounting for 29 cases (47.5%), followed by varicella in 11 patients (18%) and pneumococci in 9 (14.8%). CSF bacterial culture yield was low, positive only in 8 (3%) out of 259 cases, and matched with FA-ME panel in only one sample that grew Streptococcus pneumoniae. Bacterial culture yielded seven pathogens in those whose FA-ME panels were negative. Conclusion: FA-ME panel improves diagnostic yield as compared to bacterial culture (26.3 vs 3%). FA-ME test helps in the early initiation of targeted antibiotic therapy and greater antibiotic de-escalation.