AbstractObjectiveEpilepsy surgery is an effective treatment for drug‐resistant patients. However, how different surgical approaches affect long‐term brain structure remains poorly characterized. Here, we present a semiautomated method for quantifying structural changes after epilepsy surgery and compare the remote structural effects of two approaches, anterior temporal lobectomy (ATL), and selective amygdalohippocampectomy (SAH).MethodsWe studied 36 temporal lobe epilepsy patients who underwent resective surgery (ATL = 22, SAH = 14). All patients received same‐scanner MR imaging preoperatively and postoperatively (mean 2 years). To analyze postoperative structural changes, we segmented the resection zone and modified the Advanced Normalization Tools (ANTs) longitudinal cortical pipeline to account for resections. We compared global and regional annualized cortical thinning between surgical treatments.ResultsAcross procedures, there was significant cortical thinning in the ipsilateral insula, fusiform, pericalcarine, and several temporal lobe regions outside the resection zone as well as the contralateral hippocampus. Additionally, increased postoperative cortical thickness was seen in the supramarginal gyrus. Patients treated with ATL exhibited greater annualized cortical thinning compared with SAH cases (ATL: −0.08 ± 0.11 mm per year, SAH: −0.01 ± 0.02 mm per year,t= 2.99,P= 0.006). There were focal postoperative differences between the two treatment groups in the ipsilateral insula (P= 0.039, corrected). Annualized cortical thinning rates correlated with preoperative cortical thickness (r= 0.60,P< 0.001) and had weaker associations with age at surgery (r= −0.33,P= 0.051) and disease duration (r= −0.42,P= 0.058).SignificanceOur evidence suggests that selective procedures are associated with less cortical thinning and that earlier surgical intervention may reduce long‐term impacts on brain structure.