OBJECTIVES: To compare the health-related quality of life (HRQOL) of youths on injection regimens to those prescribed insulin pump therapy and examine factors related to HRQOL in youths with type 1 diabetes. Methods An ethnically diverse group of youths (n = 160, ages 5-17 years) with type 1 diabetes and their caretakers completed family, parent, and child adjustment measures, as well as measures of generic- and disease-specific HRQOL. Metabolic control and regimen information were assessed through medical records. Results HRQOL was unrelated to regimen prescription. Child, family, and parent adjustment variables were significantly related to HRQOL, whereas other demographic and clinical variables were relatively less important. Conclusions Present findings indicate that insulin pump therapy does not have negative implications for HRQOL. They also suggest that interventions aiming to improve HRQOL in this population should target child, parent, and family adjustment and not focus solely on disease-related outcomes.