ObjectiveLennox‐Gastaut syndrome (LGS) is a severe form of epileptic encephalopathy, presenting during the first years of life, and is very resistant to treatment. Once medical therapy has failed, palliative surgeries such as vagus nerve stimulation (VNS) or corpus callosotomy (CC) are considered. While CC is more effective than VNS as the primary neurosurgical treatment for LGS associated drop attacks, there is limited data regarding the added value of CC following VNS. This study aimed to assess the effectiveness of CC preceded by VNS.MethodsThis multinational, multicenter retrospective study focuses on LGS children that underwent CC before the age of 18 years, following prior VNS, which failed to achieve satisfactory seizure control. Collected data included epilepsy characteristics, surgical details, epilepsy outcomes, and complications. The primary outcome of this study was a reduction of 50% drop attacks.Results127 cases were reviewed (80 males). The median age at epilepsy onset was 6 months, IQR (3.12, 22.75). The median age at VNS surgery was 7 years, IQR (4, 10), and CC was performed at a median age of 11 years, IQR (8.76, 15). The dominant seizure type was drop attacks (tonic or atonic) in 102 patients. 86 patients underwent a single‐stage complete CC, and 41 an anterior callosotomy. Ten patients who did not initially have a complete CC underwent a second surgery for completion of CC due to seizure persistence. Overall, there was at least a 50% reduction in drop attacks and other seizures, in 83% and 60% respectively. Permanent morbidity occurred in 1.5%, with no mortality.SignificanceCC is vital in seizure control in children with LGS who failed VNS. Surgical risks are low. A complete CC has a tendency towards better effectiveness than anterior CC for some seizure types.