A variety of surgical treatments for intractable epilepsy with hypothalamic hamartoma (HH) are described, although most are derived from limited patient experience gathered from several centres. We describe the results of transcallosal resection of HH in 29 consecutive patients undergoing surgery at one centre. Twenty-nine patients aged 4-23 years (mean 10 years) underwent HH surgery with a minimum of 12 months follow-up. A comprehensive, presurgical epilepsy evaluation, supplemented with endocrine and ophthalmological assessments was performed in all cases. HH were resected via a transcallosal, interforniceal approach to the third ventricle, with the assistance of frameless stereotaxy, limiting the resection to the margins of the third ventricular walls and floor and minimising traction and diathermy. Complete or near-complete (>95%) resection of the HH was achieved in 18/29 patients, 75-95% resection was achieved in seven patients (four of whom had complete or near-complete disconnection of residual HH) and less than 50% resection was achieved in four. Postoperatively (follow-up 12-70 months, mean 30 months), 15 became seizure-free (nine off antiepileptic medication), seven had >90% reduction in seizure frequency, three had 55-80% reduction in seizure frequency, and four had less than 40% reduction in seizure frequency. Of 16 patients who had seizures in the early postoperative period, six became seizure. No patient or lesion characteristics were associated with postoperative seizure freedom, including features of symptomatic generalised epilepsy. Neurobehavioural improvement and resolution of EEG abnormalities were seen in the majority. Complications were transient hemiparesis in two, transient hypernatraemia in 17, short-term memory impairment in 14 (persistent in four), weight gain in ten (persistent in five), need for supplemental thyroxine in five, and lowered growth hormone (uncertain clinical significance) in six. Transcallosal resection of HH is an effective treatment for intractable epilepsy, with 76% patients in our seizures being seizure-free or having >90% seizure reduction. The operative risks include stroke, short-term memory disturbance, weight gain and minor endocrine disturbances. Based on published data, the transcallosal approach appears to be safer and more effective than other operative strategies.