OBJECTIVE: Corpus callosotomy remains an established surgical treatment for certain types of medically refractory epilepsy in pediatric patients. While the traditional surgical approach is often well tolerated, the advent of MR-guided laser interstitial thermal therapy (LITT) provides a new opportunity to ablate the callosal body in a minimally invasive fashion and minimize the risks associated with an open interhemispheric approach. However, the literature is sparse regarding the comparative efficacy and safety profiles of open corpus callosotomy (OCC) and LITT callosotomy. To this end, the authors present a novel retrospective analysis comparing the efficacy and safety of these methods. METHODS: Patients who underwent OCC and LITT callosotomy during the period from 2005 to 2018 were included in a single-center retrospective analysis. Patient demographic and procedural variables were collected, including length of stay, procedural blood loss, corticosteroid requirements, postsurgical complications, and postoperative disposition. Pre- and postoperative seizure frequency (according to seizure type) were recorded. RESULTS: In total, 19 patients, who underwent 24 interventions (16 OCC and 8 LITT), were included in the analysis. The mean follow-up durations for the OCC and LITT cohorts were 83.5 months and 12.3 months, respectively. Both groups experienced reduced frequencies of seizure and drop attack frequency postoperatively. Additionally, LITT callosotomy was associated with a significant decrease in estimated blood loss and decreased length of pediatric ICU stay, with a trend of shorter length of hospitalization. CONCLUSIONS: Longer-term follow-up and a larger population are required to further delineate the comparative efficacies of LITT callosotomy and OCC for the treatment of pediatric medically refractory epilepsy. However, the authors' data demonstrate that LITT shows promise as a safe and effective alternative to OCC.