BACKGROUND: Corpus callosotomy (CC) is a valuable palliative surgical option for children with medically refractory epilepsy due to generalized or multifocal cortical seizure onset. OBJECTIVE: To investigate the extent of CC resulting in optimal seizure control in a pediatric patient population and to evaluate the modification of seizure profile following various CC approaches. METHODS: The records of 58 children (aged 3-22 years at time of surgery) with medically refractory epilepsy who underwent CC between 1995 and 2011 were retrospectively reviewed. RESULTS: Anterior two-third callosotomy resulted in resolution of absence (p=0.03) and astatic (p=0.03) seizures, whereas anterior two-third callosotomy followed by second stage completion resulted in resolution of generalized tonic-clonic (GTC) (p=0.03), astatic (p=0.005), and myoclonic (p=0.03) seizures in addition to a trend toward resolution of absence seizures (p=0.08). Single-stage upfront complete callosotomy resulted in resolution of absence (p=0.002), astatic (p<0.0001), myoclonic (p=0.007), and complex partial seizures (p=0.008) in addition to a trend toward resolution of GTC (p=0.06). In comparing a composite of subjects who underwent anterior two-third callosotomy alone or two-stage complete callosotomy prior to the second stage to complete the callosotomy with subjects who underwent upfront complete CC, a more favorable outcome was found in those with the upfront complete CC (p=0.02). CONCLUSION: Single-stage upfront complete callosotomy is effective in relieving a broader spectrum of seizure types than anterior two-third callosotomy or two-stage complete callosotomy in children. The advantages of single stage complete callosotomy must be weighed against the potentially higher risk of neurologic and operative complications.