a b s t r a c tBackground and purpose: Novel approaches applying machine-learning methods to neuroimaging data seek to develop individualized measures that will aid in the diagnosis and treatment of brain-based disorders such as temporal lobe epilepsy (TLE). Using a large cohort of epilepsy patients with and without mesial temporal sclerosis (MTS), we sought to automatically classify MTS using measures of cortical morphology, and to further relate classification probabilities to measures of disease burden. Materials and methods: Our sample consisted of high-resolution T1 structural scans of 169 adults with epilepsy collected across five different 1.5 T and four different 3 T scanners at UCLA. We applied a multiple support vector machine recursive feature elimination algorithm to morphological measures generated from FreeSurfer's automated segmentation and parcellation in order to classify Epilepsy patients with MTS (n = 85) from those without MTS (N = 84). Results: In addition to hippocampal volume, we found that alterations in cortical thickness, surface area, volume and curvature in inferior frontal and anterior and inferior temporal regions contributed to a classification accuracy of up to 81% (p = 1.3 × 10 −17 ) in identifying MTS. We also found that MTS classification probabilities were associated with a longer duration of disease for epilepsy patients both with and without MTS. Conclusions: In addition to implicating extra-hippocampal involvement of MTS, these findings shed further light on the pathogenesis of TLE and may ultimately assist in the development of automated tools that incorporate multiple neuroimaging measures to assist clinicians in detecting more subtle cases of TLE and MTS.