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Health-related quality of life (HRQOL) is an important outcome measure in clinical research. Given the psychosocial and behavioral difficulties associated with pediatric epilepsy, evaluating HRQOL in this patient population is of particular importance. Though HRQOL has been examined in pediatric patients receiving focal resection or pharmacological (antiepileptic drug; AED) treatment, it has not been assessed in patients receiving hemispherectomy (HE) for intractable epilepsy. The current study evaluated HRQOL in a sample of pediatric HE cases (N=26) using previously validated questionnaires relative to surgical (N=30) and nonsurgical (N=84) comparison groups. Compared with focal resection and nonsurgical patients, parents of children who received HE reported similar levels of HRQOL. In surgical cases, worse HRQOL was correlated with residual seizure frequency. In both surgical and nonsurgical cases, female gender, higher AED load, and lower functional independence predicted worse HRQOL. Interestingly, HE status (i.e., having undergone HE) predicted fewer epilepsy-related limitations. Consistent with previous findings, AED load, in addition to lower functional abilities, appear particularly detrimental to life quality in pediatric epilepsy. HE, however, is not associated with increased risk for poor HRQOL. When considered in light of the multiple, significant risk factors for poor outcome associated with HE, children who undergo the procedure fare surprisingly well.