PURPOSE The goal of the study was to assess the outcome of antiepileptic drug (AED) withdrawal in children and adolescents with cryptogenic focal epilepsies (CFE). METHODS Medical records of consecutive patients with CFE from two referral hospitals were retrospectively evaluated over a nine-year period. Inclusion criteria were: (1) diagnosis of CFE according to the ILAE criteria, (2) less than 16 years of age at onset of epilepsy, (3) established clinical remission of at least two years before AED withdrawal, and (4) follow-up period of at least two years after withdrawal (or until seizure relapse in patients who relapsed). Time to seizure relapse and predictive factors were analyzed by survival methods. RESULTS The cohort consisted of 52 patients (16 females, 36 males). Relapse rate was 37.85%. Most relapses occurred during the first 12 months after withdrawal. Univariate analyses indicated the following factors as significantly correlated with seizure recurrences: (1) female sex; (2) age at withdrawal of AED 14 years or higher; (3) abnormal EEG before withdrawal; and (4) abnormal EEG during and after AED withdrawal. Multivariate Cox regression analyses revealed that female sex, age at withdrawal of AED 14 years or higher; and abnormal EEG during and after withdrawal were significant independent predictive factors for seizure recurrences. CONCLUSION The relapse rate in our cohort was similar to the most commonly reported overall rates for childhood-onset epilepsy. Distinguishing variables-female sex, age at withdrawal greater than 14 years, and abnormal EEG - need to be considered when choosing and further following of eligible candidates for AED withdrawal.