Objective: Intravenous immunoglobulin and plasma exchange are proven treatments for Guillain-Barre syndrome. Despite these treatments, the prognosis for severe Guillain-Barre syndrome is still not satisfactory. This article seeks for a logical timing for plasma exchange-intravenous immunoglobulin synergy, which may improve outcome in severe Guillain-Barre syndrome requiring mechanical ventilation. Study Design: This study is an open-label study. Nine pediatric severe Guillain-Barre syndrome patients requiring mechanical ventilation were treated with novel treatment strategy named as "zipper method." In this method, following diagnosis of Guillain-Barre syndrome, plasma exchange was started immediately. In the first session of plasma exchange, one and a half volume of patients' plasma was removed by using 5% albumin as replacement solution. At the end of the plasma exchange session, 0.4 g/kg intravenous immunoglobulin infusion was started immediately. Second plasma exchange session was applied with one volume change after 24 hours from the end of the intravenous immunoglobulin infusion. Each plasma exchange session was followed by intravenous immunoglobulin infusions. This plasma exchange-intravenous immunoglobulin cycle was repeated for 5 times. Results: Among the 9 patients, the mean mechanical ventilation duration was 7 (5-14) days and the mean hospital stay was 18 (10-30) days. Medical Research Council sum score was increased in all patients, especially after the third session. All patients survived and all patients were able to walk unaided on the 28th day of admission. Conclusion: The zipper method as a novel treatment modality seems to reduce mortality, speed up weaning from mechanical ventilation, and shorten hospital stay, with excellent outcome in severe Guillain-Barre syndrome patients, who require intensive care. This technique stands as a promising immunomodulation strategy for various scenarios.