ABSTRACT Background and Objectives: Therapeutic plasma exchange (TPE) is commonly used as a treatment of certain autoimmune neurological diseases, and its main target is to remove pathogenical toxins or autoantibodies. Removed plasma with toxins and autoantibodies is replaced by crystalloids, colloids, and/or normal saline. It is more effective and cost-effective than immunoglobulins. The aim of this study was to know the effectiveness of TPE in autoimmune neurological diseases. Methods: This is a prospective study involving 376 autoimmune neurological cases, and the duration of this study was 5 years. All autoimmune neurological patients irrespective of age with complaints of weakness in limbs, respiratory distress, and acute myasthenia gravis (MG) crisis cases were included in the study. The Modified Rankin Score and MG Composite Score were used to analyze the severity of the disease, and the number of TPE procedures or cycles was planned. Results: The total number of cases included was 376 (322 newly registered cases and 54 old and relapse cases), and the total number of TPE procedures done was 1491 between the years 2017 and 2021. Male patients were 138 and female patients 238. The most number of cases were of MG, followed by Guillain–Barre syndrome. The mean number of TPE procedures done was 6.1 cycles in myasthenia crisis patients. There was a significant improvement in the patients after the treatment. The Modified Rankin Score and MG Composite Score were 1/6 and 3/50, respectively (P = 0.0321 and P = 0.0298, respectively) after completion of the TPE. Conclusion: TPE is the most effective method in cases of neurological autoimmune diseases. Most of the cases show improvement immediately after the first cycle, and more than half of the cases will be able to walk or do their routine activities after 2 or 3 cycles. It is a safe and cost-effective treatment modality with minimal side effects or complications.