Plasma exchange (PE) is the standard treatment in Guillain-Barré syndrome (GBS) patients who have lost the ability to walk. The effect of exchanges before this stage and the optimal number of exchanges for the other patients are still unknown. We randomized 556 GBS patients according to severity and number of exchanges as follows: Zero versus 2 PEs for patients who could walk-with or without aid-but not run, or who could stand up unaided (mild group); 2 versus 4 PEs for patients who could not stand up unaided (moderate group); and 4 versus 6 PEs for mechanically ventilated patients (severe group). In the mild group, 2 PEs were more effective than none for time to onset of motor recovery (median, 4 vs 8 days, respectively). In the moderate group, 4 PEs were more beneficial than 2 for time to walk with assistance (median, 20 vs 24 days) and for 1-year full muscle-strength recovery rate (64% vs 46%). Six PEs were no more beneficial than 4 in the severe cases. Patients with mild GBS on admission should receive 2 PEs. Patients with moderate and severe forms should benefit from 2 further exchanges.