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Introduction: Approximately 30% of patients with mesial temporal lobe epilepsy (MTLE) will develop drug resistance, which requires early surgical treatment. The success of the surgical procedure largely depends on the correct lateralisation of the epileptogenic zone, which can only be determined in 70% of patients with such conventional diagnostic tools as video electroencephalography and volumetric structural magnetic resonance imaging. We evaluated the performance of a memory functional magnetic resonance imaging (fMRI) paradigm in lateralising the epileptogenic zone in patients with drug-resistant MTLE., Methods: We included 18 patients with MTLE attended at the Instituto Neurológico Colombiano in Medellin (Colombia) between 2018 and 2019. The volume of functional activation in both temporal lobes was determined with a memory fMRI paradigm. A concordance analysis was performed to compare the performance of fMRI against that of conventional tests., Results: In patients with left MTLE, lower total activation was found in the hemisphere ipsilateral to the epileptogenic zone as compared to the contralateral hemisphere (121.15 ± 16.48 voxels vs 170.23 ± 17.8 voxels [P < .001]), showing substantial concordance with conventional tests. Patients with right MTLE displayed lower hippocampal activation ipsilateral to the epileptogenic zone (18.5 ± 3.38 voxels vs 27.8 ± 3.77 voxels in the contralateral hippocampus [P = .048]), showing moderate concordance with conventional tests., Conclusions: These findings suggest that lower functional activation as determined by a memory fMRI paradigm has a high level of concordance with conventional tests for lateralising the epileptogenic zone in patients with drug-resistant MTLE., (Copyright © 2022 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)