ObjectiveCorpus Callosotomy (CC) is an important treatment for atonic seizures in patients with generalized or multi‐focal drug‐resistant epilepsy (DRE). Traditionally, CC is performed via an open microsurgical approach, but more recently, MR‐guided stereotactic laser interstitial thermal therapy (LITT) corpus callosum ablation (CCA) has been developed to leverage the safety and minimally invasive nature of LITT. Given the recent adoption of CCA at select centers, how CCA compares to CC is unknown. We aim to compare clinical seizure outcomes of CCA to CC after extended follow‐up.MethodsWe performed a retrospective cohort study to compare the effectiveness and safety of CC to CCA from 1994‐2022. The primary outcome was the difference between 50% reduction of target seizure. Secondary outcome measures were postoperative length of stay, adverse events, and other effectiveness metrics. Comparative statistics were executed using Stata. Normality for continuous variables were assessed and parametric statistics were utilized as needed. Frequency was compared with chi‐squared or Fischer's exact tests, when applicable.ResultsData from 47 operations performed on 36 patients were included in this study, of which 13 (36%) patients underwent 17 CCA. Patients who received CCA had similar rates of meaningful reduction (>50%) of atonic seizures as their CC counterparts (55% vs 70% p=0.15). Patients undergoing CCA had significantly shorter hospitalizations than those receiving CC (2.5 vs 6.0 days p<0.001). There was no significant difference in rates of post‐operative complications between the groups, although the magnitude of the complication rates was lower in the CCA cohort (12% vs 28%).SignificanceThis early experience suggests CCA has similar outcomes to traditional CC, albeit with shorter hospital length of stay. However, future studies are necessary to investigate non‐inferiority between these two approaches. Large multi‐center studies are necessary to investigate differences in adverse events and whether these findings generalize across other centers.