Hypothalamic hamartomas (HHs) are typically associated with pharmacologically intractable gelastic seizures, which often develop into complex partial and/or generalized tonic–clonic seizures. The transcallosal, anterior interforniceal (TAIF) approach to HH resection has been shown to be safe and to result in good seizure frequency reduction. We documented postsurgical cognitive functioning and examined whether using the TAIF approach with older adolescents and adults affected long-term cognitive outcome. Six older adolescents and adults, who had undergone resection of an HH using the TAIF approach, underwent comprehensive neuropsychological assessment at least 2years postoperatively. Four of these individuals also had neuropsychological evaluation preoperatively. All participants who were assessed pre- and postoperatively demonstrated long-term improvement in perceptual/visuospatial function after surgery. Three of the four participants also demonstrated lasting reduction in memory function postoperatively. The TAIF approach to HH resection is associated with a high risk of long-term memory impairment in older adolescents and adults.