Hypothalamic hamartomas (HH) may induce drug-resistant epilepsy (DRE), thereby requiring surgical treatment. Conventionally, treatment is aimed at removing the lesion, but a disconnection procedure has been shown to be safer and at least as effective. The thulium laser (Revolix) has been recently introduced in urological endoscopy because of its ability to deliver a smooth cut with good control of the extent of tissue damage. The authors sought to analyze the safety and efficacy of the thulium 2-μm laser applied through navigated, robot-assisted endoscopy in disconnection surgery for HHs. Twenty patients with HH who were drug resistant were treated during a 12-month period. Conventional disconnection by monopolar coagulation (endoscopic electrode) was performed in 13 patients, and thulium laser disconnection was performed in the remaining 7 patients. The endoscope was inserted into the ventricle contralateral to the attachment of the HH on the third ventricular wall. Results in terms of safety, efficacy, and ease of use of the instrument were analyzed. All 20 patients achieved a satisfactory postoperative Engel score (Classes I-III). At 12 months, the Engel class was I or II in 8 of 13 patients (61.5%) who underwent monopolar coagulation and in 6 of 7 patients (85.7%) who underwent laser disconnection (p = 0.04). Seven of 13 patients (53.8%) who underwent monopolar coagulator disconnection and 2 of 7 patients (28.6%) who underwent laser disconnection had immediate postoperative complications. At the 3-month follow-up, only 2 patients (15.4%) treated by coagulation still experienced mild surgery-related recent memory deficits. No complications persisted at the 12-month follow-up. The disconnection procedure is a safe and effective treatment strategy to treat drug-resistant epilepsy in patients with HHs. With the limitations of initial experience and a short-term follow-up, it appears that the thulium 2-μm laser has the technical features to replace the standard coagulation in this procedure.