Clinical seizure semiology can provide important information on the lateralization of the epileptogenic zone. We investigated factors associated with clinical seizure lateralization in patients with pathologically proven mesial temporal sclerosis. We reviewed 243 seizures of 58 patients. Clinical lateralization was possible in 155 (63.8%) of 243 seizures. Lateralization was correct in 144 (92.9%) of 155 lateralized seizures. Logistic regression analysis showed that age at onset (p = 0.001; odds ra tio = 1.089, 95% confidence interval = 1.035-1.145) and the contralateral propagation pattern of ictal discharges (p = 0.001; odds ratio = 3.544, 95% confidence interval = 1.723-7.289) correlated with clinical seizure lateralization. The patient group with clinically lateralized seizures had a younger age at onset of habitual seizures compared to the clinically nonlateralized group (11.1 +/- 6.3 vs. 15.6 +/- 8.4 years; p < 0.001). Of seizures without bitemporal asynchrony or switch of lateralization, 70.7% were clinically lateralized compared with only 46.4% of seizures with asynchrony or lateralization switch. The present results suggest that the age of epilepsy onset and the ictal scalp EEG propagation pattern affect clinical seizure lateralization in patients with mesial temporal sclerosis.