Background Immunomodulation, including IVIG and plasma exchange, is useful for a crisis or severe exacerbation. Plasma exchange may be slightly faster and more effective in a myasthenic crisis than IVIG. The aim of the current study was to determine the changes in the quality of life (QOL) after plasmapheresis and factors influencing these changes. Results This study was conducted on 98 MG patients diagnosed as moderate to severe myasthenia gravis (according to Myasthenia Gravis Foundation of America classification), 81 patients received alternate day 5 sessions plasmapheresis (TPE group) and 17 patients were on medical treatment only (control group). All patients were subjected to full history, through clinical neurological evaluation and scored with quantitative myasthenia gravis (QMG) score for MG severity at start and after 1 m. Both groups completed the QOL questionnaire at baseline and after 1 month. The MG-QOL-15 scores were computed and we analyzed the change in the QOL scores from baseline to after plasmapheresis groups and compared it with the results for the control group. The scores in QOL scales had significantly decreased after plasmapheresis, and the improvement in QOL scores had a good correlation with the decrease in QMGS. The improvement in QOL and QMG was significantly correlated with younger age, female gender, shorter duration of the illness, presence of AchR antibodies, antibody titer, and thymus hyperplasia. Conclusion Plasmapheresis is effective in improving quality of life in myasthenia gravis patients and this improvement influenced by age, gender, duration of illness, presence of AchR antibodies and their titer, and the thymus pathology.