Background: The first-line treatment for people with acute mania, mood disorders, severe depression, and catatonia is electroconvulsive therapy (ECT). The goal of anesthesia during ECT is to cause unconsciousness, and the drugs administered should not have any effect on seizures. Because all anesthetics have some ability to change seizures, the kind of anesthetic used in modified ECT becomes crucial. This study aimed to assess the hemodynamic profile during modified ECT and the effects of ketamine and thiopentone sodium on seizure duration. Aims and Objectives: The aim of the study was to compare the outcome of ECT, such as hemodynamics, improvement in depression, and duration of seizure, with ketamine versus thiopentone sodium in depressive disorder. Materials and Methods: A prospective observational study was conducted with 50 randomly selected depression patients after obtaining permission from the Institutional Ethics Committee and consent from the patients and attendants from June 2021 to November 2022. All 50 cases were equally divided into group K and group T. To obtain the data, a predesigned, semi-structured questionnaire was used along with the Hamilton rating scale for depression and ECT. The Chi-square test was used to measure the association between two categorical variables. A P < 0.05 was considered statistically significant. Results: The mean heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, and saturation of peripheral oxygen are higher in group K than in group T, and the mean difference was significant between group K and group T. Groups had a statistically significant association with increased secretions, nausea and vomiting, and headache, but not with gender, ASA grade, and number of ECT sessions. Conclusion: Compared to ketamine, thiopentone sodium was found to have minimal hemodynamic derangements, a decrease in seizure duration, and side effects.