Introduction: To characterize pretreatment behavioral problems and differential effects of initial therapy in children with childhood absence epilepsy (CAE). Methods: The Child Behavior Checklist (CBCL) was administered at baseline, week ۱۶- ۲۰, and month ۱۲ visits of a randomized double-blind trial of ethosuximide, lamotrigine, and valproate. Total problems score was the primary outcome measure. Results: A total of ۴۵۰ participants at baseline, ۳۵۰ participants at the week ۱۶-۲۰ visit, and ۱۰۰ participants at the month ۱۲ visit had CBCL data. At baseline, ۹% (۹۵% confidence interval [CI] ۶%-۱۳%) of children with CAE had elevated total problems scores (mean ۵۴.۹±۱۰.۹۵). At week ۱۶-۲۰, participants taking valproic acid had significantly higher total problems (۵۱.۲ [۹۸.۵% CI ۴۸.۶-۵۸.۷]), externalizing problems (۵۱.۵ [۹۸.۷% CI ۴۸.۵-۵۴.۵]), attention problems (۵۷.۸ [۹۸.۳% CI ۵۵.۶-۶۰.۰]), and attention-deficit/hyperactivity problems (۵۵.۸ [۹۸.۵% CI ۵۴.۱-۵۷.۹]) scores compared to participants taking ethosuximide (۴۶.۸ [۹۸.۳% CI ۴۳.۴-۴۹.۶]; ۴۵.۸ [۹۸.۳% CI ۴۲.۹-۴۸.۷]; ۵۴.۶ [۹۸.۳% CI ۵۲.۴-۵۶.۹]; ۵۳.۰ [۹۸.۳% CI ۵۱.۳-۵۴.۸]). Lack of seizure freedom and elevated week ۱۶-۲۰ Conner Continuous Performance Test confidence index were associated with worse total problems scores. At month ۱۲, participants taking valproic acid had significantly higher attention problems scores (۵۷.۹ [۹۸.۳% CI ۵۵.۶-۶۰.۳]) compared to participants taking ethosuximide (۵۴.۵ [۹۵% CI ۵۲.۱-۵۶.۹]). Conclusions: Pretreatment and ongoing behavioral problems exist in CAE. Valproic acid is associated with worse behavioral outcomes than ethosuximide or lamotrigine, further reinforcing ethosuximide as the preferred initial therapy for CAE. This study provides Class II evidence that for children with CAE, valproic acid is associated with worse behavioral outcomes than ethosuximide or lamotrigine.