Background and Objectives: The procedure of removal of pathologic substances present in the plasma of the patients and its substitution with a suitable replacement fluid is known as therapeutic plasma exchange (TPE). It has been seen that this procedure has an ameliorating effect on the clinical condition of the patient of Guillain-Barré syndrome (GBS). This study aims to assess the clinical improvement in GBS patients treated with TPE at a tertiary care center. Methods: A retrospective chart review was conducted in a series of 57 GBS patients treated with TPE using an intermittent flow cell separator system. GBS disability and Medical Research Council (MRC) muscle strength scoring systems were used as final endpoints. Statistical analysis was done through the R software version 3.2.0. A value of P < 0.05 was considered to be statistically significant. Results: After 05 alternate day cycles, TPE treatment led to a significant improvement in both MRC muscle strength scores and GBS disability scores. Before TPE, the MRC muscle strength score was 1.38 ± 1.19 (range: 0–4) and this increased to 3.15 ± 1.57 (range: 0–5) after TPE, (P = 0.002). Similarly, before TPE, the mean GBS disability score was 4.00 ± 0.81 (range: 2–5) and this decreased to 2.69 ± 1.31 (range: 1–5) after TPE, (P = 0.003). Conclusion: The result of this study showed TPE to be an effective mode of treatment for GBS. The safety profile was found to be acceptable and going by the findings of this study, TPE must be considered as an early line of management.