Background: Therapeutic plasma exchange (TPE) is a conventional second-line treatment for patients with multiple sclerosis (MS) or clinically isolated syndrome with steroid-refractory relapses.Methods: MS and clinically isolated syndrome patients with a steroidrefractory relapse, who fulfilled the indications for TPE were enrolled in this study. An expert nurse recorded the data comprising age, sex, type of MS, disease modifying therapy, disease duration, relapse rate, vital signs at the beginning, during and at the end of each plasma exchange session, plasma exchange volume, normal saline volume, and TPE complications. Ultimately, the statistical association was estimated amongst the variables.Results: A total of 122 cases were assessed. Twelve cases (9.8%) received plasmapheresis for the second time. The mean age was 32.2 8.7 years and 107 (87.7%) were female. In total, 609 plasma exchange sessions were completed. Hypotension and skin reaction were the most clinical complications. Hemoglobin loss and hypokalemia were the most laboratory complications. Fifty-four cases (44.3%) had no complications, 40 (32.8%) had 1 complication, 21 (17.2%) 2 complications, 6 (4.9%) had 3 complications, and 1 (0.8%) disclosed 4 complications. The relapse rate in the past 12 months and the mean plasma volume exchange were significantly different between the groups.Conclusions: We revealed that TPE could be considered as a safe secondline therapy in MS relapses. Hypotension, skin reaction, hemoglobin loss, and hypokalemia were the most complications of TPE in our patients.