Traumatic brain injury (TBI) is a leading cause of pediatric disability. Although persistent pain has been recognized as a significant postinjury complication, there is a paucity of data concerning the postinjury pain experience of youth. This study aimed to examine the prevalence of persistent pain in adolescents after TBI, identify risk factors for pain, and evaluate the impact of pain on adolescent health-related quality of life. Participants included 144 adolescents with mild to severe TBI who were followed over 36 months after injury. At 3-, 12-, 24-, and 36-month assessments, measures of pain intensity, depression, posttraumatic stress disorder, and health-related quality of life were completed by adolescents. Findings demonstrated that 24.3% of adolescents reported persistent pain (defined as usual pain intensity ≥3/10) at all assessment points after TBI. Female sex (odds ratio = 2.73, 95% confidence interval = 1.12-6.63) and higher levels of depressive symptoms at 3 months after injury (odds ratio = 1.26, 95% confidence interval = 1.12-1.43) were predictors of persistent pain at 36 months. Furthermore, mixed linear models indicated that early pain experience at 3 months following TBI was associated with a significantly poorer long-term health-related quality of life. CONCLUSIONS This is the first study to examine the prevalence of persistent pain over long-term follow-up in adolescents after TBI and its impact on health-related quality of life. These findings indicate that adolescents with TBI may benefit from timely evaluation and intervention to minimize the development and impact of pain.