Context: Autoimmune encephalitis (AE) is an emerging cause of non-infective encephalitis, presentations of which vary widely. Traditionally the diagnosis of AE is based on detection of antibodies in a patient with clinical picture suggestive of AE., Aim: To evaluate the clinical characteristics and response to immunotherapy in patients with antibody negative autoimmune encephalitis and to compare them with definite cases., Settings and Design: A prospective follow-up study was done in patients presenting with presumptive symptoms of AE from January 2017 to January 2019. The study was done in a tertiary care institute of Northern India., Patients and Methods: Demographic and clinical parameters were noted and relevant investigations for management were done according to well-defined protocol. The patients were treated with immunomodulatory therapy in the form of steroids and/or intravenous immunoglobulins (IVIg). They were followed up for treatment response and relapse at 2 monthly intervals., Statistical Analysis Used: The data was expressed as either proportions or mean/median. Chi-square test/Independent T test was used to compare antibody positive and antibody negative group., Results: Out of 31 patients with presumptive AE, 16 patients tested positive for autoimmune antibodies (definite AE). Incidences of seizure, behavioral abnormalities, dementia and altered sensorium were similar between the 2 groups ( p > 0.05). Complete or partial response was seen in all treated patients in both groups with no significant difference ( p 0.716). CSF protein concentration and cellularity were higher in the definite group although only high protein concentration could reach statistical significance ( p 0.002). Malignancy could be confirmed after extensive search in 2 out of 16 patients with definite AE and in 1 out of 15 antibody negative AE patients., Conclusions: Clinical presentation of antibody negative cases does not differ significantly from definite ones. Since treatment response is also similar in both the groups, starting immunotherapy in a patient presenting with presumptive symptoms of AE, while ruling out other common mimickers, seems to be the need of the hour in the management of this evolving entity., Competing Interests: There are no conflicts of interest., (Copyright: © 2006 - 2019 Annals of Indian Academy of Neurology.)