Objective: The main aim of our study was to investigate the handedness of patients with mesial temporal lobe epilepsy (MTLE). We also sought to identify clinical variables that correlated with left-handedness in this population. Methods: Handedness (laterality quotient) was assessed in 73 consecutive patients with MTLE associated with unilateral hippocampal sclerosis (HS) using the Edinburgh Handedness Inventory. Associations between rightand left-handedness and clinical variables were investigated. Results: We found that 54 (74.0%) patients were right-handed, and 19 (26%) patients were left-handed. There were 15 (36.6%) left-handed patients with left-sided seizure onset compared to 4 (12.5%) left-handed patients with right-sided seizure onset (p = 0.030). Among patients with left-sided MTLE, age at epilepsy onset was significantly correlated with handedness (8 years of age [median; min-max 0.5-17] in left-handers versus 15 years of age [median; min-max 3-30] in right-handers (p < 0.001). Conclusions: Left-sided MTLE is associatedwith atypical handedness, especiallywhen seizure onset occurs during an active period of brain development, suggesting a bi-hemispheric neuroplastic process for establishing motor dominance in patients with early-onset left-sided MTLE. (C) 2017 Elsevier Inc. All rights reserved.