Objectives: To assess whether intravenous immunoglobulin (IVIG) followed by plasma exchange (PE) is more effective for patients with Guillain-Barré syndrome compared with IVIG alone. Methods: Retrospective chart review of 46 patients treated for Guillain-Barré syndrome between 1995 and 2005 was performed. Patients were divided into four subgroups based on treatment received (IVIG, PE, IVIG + PE, or neither). Disability grade on admission, after completion of IVIG, and on the day of discharge from hospital (DGD) were assessed. DGD was the primary outcome measure. Duration of hospitalization, costs, duration of symptoms before treatment, and interval between IVIG and initiation of PE were analyzed. Results: Mean disability grade on admission was similar for all groups. DGD was significantly lower for the IVIG group (P < 0.001) than other groups. Compared with admission, patients treated with IVIG + PE had more severe impairment after completion of IVIG (P = 0.044) but did not show significant improvement after PE. Disability grade on admission and DGD scores for patients treated earlier (less than 14 days after onset of symptoms) versus later (greater than 14 days) were not significantly different. Duration of hospitalization was longer in patients receiving IVIG + PE versus IVIG alone (P < 0.001). The cost of treatment was significantly higher in the IVIG + PE subgroup (P < 0.001). No correlation between interval from IVIG to PE onset and DGD score was found. Conclusions: We found no association between PE after IVIG and improved short-term outcomes of patients with Guillain-Barré syndrome, but there was an association with an increase in cost and duration of hospitalization. There was no association between the timing of PE after IVIG and the short-term outcome. Prospective studies are needed to clarify whether the cost/benefit ratio favors the routine use of this therapeutic approach.