Background The numbers of children with long‐term illnesses surviving into adulthood and transferring from child to adult services has increased dramatically in the last 30 years. This study aimed to examine health‐related quality of life pre‐ and post‐transfer from child to adult healthcare for young people with three long‐term illnesses. Methods A total of 217 young people with cystic fibrosis, congenital heart defects or diabetes attending child and adult hospital services in Dublin, Ireland completed a questionnaire survey. Multiple linear regression was used to identify predictors of five dimensions of health‐related quality of life pre‐ and post‐transfer. Results Post‐transfer young people with congenital heart disease and diabetes reported significantly lower physical well‐being than their pre‐transfer counterparts. Pre‐transfer young people with cystic fibrosis reported significantly lower physical well‐being than those with diabetes, but there was no significant difference post‐transfer. Pre‐transfer females reported lower scores than males on the Psychological Well‐being and Autonomy and Parent Relation dimensions; however, these differences disappeared post‐transfer. Higher maternal overprotection scores were associated with significantly lower scores on the Psychological Well‐being, Autonomy and Parent Relation, and Social Support and Peers dimensions, regardless of transfer status. Conclusions Disease group, gender and maternal overprotection were predictors of health‐related quality of life pre‐ and post‐transfer from child to adult healthcare. Transition programmes should promote self‐management and discourage parental overprotection.