Background: Previous reports have shown that about one-third of major depressive disorder (MDD) patients failed to respond to existing antidepressants therapy. Those who respond take months to attain a significant effect. Ketamine is receiving attention for the treatment of depression. Patients using ketamine get relief from depression within 24 hours of use. Ketamine infusion therapy can be an effective treatment of depression symptoms under the medical supervision. Aims and Objective: To study the role of ketamine in MDD. Materials and Methods: This is five weeks observational study on 20 patients of MDD. On day one, first all of study patients received a 40-min IV dose of ketamine (0.5 mg/kg) under supervision of doctor, with continuous monitoring of vital-signs. Based on response from previous next doses were administered till the patients shows positive signs of the treatment. Results: Ketamine caused minimal positive psychotic symptoms; six patients out of 20 have shown significant but temporary dissociative symptoms. Mild side effects were recorded during and after each ketamine infusion. Out of 20 subjects 18 have met the response after the first and the 6^th IV of ketamine. MADRS scores after the 7th infusion was 85% (±12%). After ketamine infusion 18 of 20 patients relapsed on average of 20 days after the sixth infusion between 7 to 50 days. Post ketamine treatment two patients remained without antidepressant with minimal symptoms of depression for more than 4 months. Conclusion: Finding of this suggest the feasibility with positive outcomes of ketamine for the treatment of MDD.