40% of children with epilepsy fell in at-risk trajectories for overall health-related quality of life (HRQOL).

Most subscale models contained at least one at-risk trajectory containing up to 78% of children with epilepsy.

Many of the HRQOL trajectories appeared stable during the two years following epilepsy diagnosis and AED initiation.

Number of AEDs, Internalizing Problems, and Externalizing Problems emerged as consistent predictors across domains.

Interventions should target modifiable factors shortly after diagnosis to improve HRQOL for children with epilepsy.