Objective: Pediatric drug-resistant epilepsy (DRE) is associated with poor health-related quality of life (HRQOL). Achieving seizure control, however, does not improve HRQOL in all children. This study sought to evaluate whether (1) baseline caregiver and family factors are associated with child HRQOL at 1-year follow-up over and above epilepsy characteristics, treatment, and seizure outcome; and (2) baseline family factors moderate the association between seizure outcome and child HRQOL at 1-year follow-up. Methods: This multicenter longitudinal cohort study recruited 152 children with DRE who were being evaluated for surgical candidacy. Child HRQOL was rated by caregivers using the Quality of Life in Childhood Epilepsy Questionnaire at baseline and 1-year follow-up. Additional data collected at baseline included child epilepsy characteristics, caregiver demographics, caregiver mood, and family environment. Results: Seizure freedom was achieved in 68% and 28% of patients 1 year after surgery and medical treatment, respectively. Caregiver and family factors were not associated with higher child HRQOL at follow-up after accounting for epilepsy characteristics, treatment, seizure outcome, and baseline child HRQOL, F 11, 131 = 1.34,