Introduction Electroconvulsive therapy (ECT) is a functional treatment for a significant mental illness that involves a momentary application of electrical stimulation to induce generalized seizures. The use of right unilateral (RUL) and bilateral (BL) ECT has been controversial. Thus, the study aimed at comparing the effectiveness of RUL ECT and BL ECT in treating depression. Methodology A longitudinal study was conducted between September 2016 and January 2021 at a tertiary care hospital in Sindh, Pakistan. All patients over the age of 18 with clinically diagnosed depression in the last month were included in the study. Baseline depression scores and post-treatment scores were determined using Hamilton Depression Rating Scale (HDRS). All patients were assigned to each treatment group. Group A was administered right unilateral electroconvulsive therapy, while group B was administered bilateral electroconvulsive therapy. Adverse effects were documented right after treatment, at four hours, and then one day after therapy. Depression severity was determined after each ECT session using the HDRS scale. Electroconvulsive therapy was discontinued when an HDRS score of 10 was achieved.  Results  The mean HDRS score at baseline in the bilateral ECT group was 24.99 ± 3.938, which lowered to 17.56 ± 2.65 by the 3rd session, 12.45 ± 3.76 by the 6th session, and to 11.86 ± 2.3 by the end of treatment (p<0.0001). Similarly, the right unilateral ECT was equally effective in improving the depressive symptoms (p<0.0001). There was no significant difference between the efficacy of bilateral and unilateral placements of electrodes in electroconvulsive therapy (p=0.116).