Objectives:: Demyelinating diseases of central nervous system (CNS) are a broad spectrum of conditions with autoimmune process against myelin. In a resource limited country like India, it is imperative to perform proper clinical evaluation, neuroimaging to differentiate among various categories of CNS demyelinating diseases to decide regarding further workup and treatment. The objective of our study was to determine clinical presentation, imaging findings, serology results, diagnosis, and treatment outcome of primary demyelinating disorders of CNS. Materials and Methods:: In this prospective study, a total of 44 patients were enrolled over a period of 1 year. After proper evaluation, patients were categorized into different groups applying newer diagnostic criteria. Patients were treated with steroids, appropriate immunomodulatory therapy, and outcomes were analyzed. Results:: The majority of cases were of neuromyelitis optica spectrum disorder (NMOSD) (45.5%) with an overall female-to-male ratio of 3.4:1 and mean age of presentation was 30.5 ± 11.15. Myelitis (52.3%) followed by optic neuritis (45.5%) was the most common initial presentation. The most common site of involvement on magnetic resonance imaging was the spinal cord (particularly the cervicodorsal cord). The majority showed good response to therapy (77.27%) and two patients did not survive. Conclusion:: Higher disability observed among seropositive NMOSD patients warrants aggressive treatment during the first attack itself. It is important to suspect myelin oligodendrocyte glycoprotein antibody disease in patients with preceding viral infection. A good outcome in the majority is likely due to the availability of serological assays and aggressive immunomodulatory therapy.