Adherence to treatment recommendations following medical care for pediatric conditions is critically important for promoting optimal physical and psychological well-being. While it has been a focus of many studies across pediatric chronic illness populations, there is a dearth of research examining adherence following pediatric unintentional injury. Empirical evidence from studies with pediatric chronic illness samples indicates that youth experience a number of barriers to adherence to medical recommendations. Adherence is especially difficult for adolescents due to the unique challenges of this developmental period. A mixed methods research approach was utilized to gain a holistic understanding of potential psychological barriers to adherence following adolescent injury. Quantitative analyses examined the potential predictive roles of adolescent psychological [i.e., posttraumatic stress (PTSD), depression, quality of life] and relational (i.e., parent PTSD and depression) factors on adherence. Results of analyses were insignificant; thus, qualitative data was collected to deepen the understanding of barriers to adherence. Findings from qualitative data analyses suggested that a number of barriers to adherence to treatment recommendations exist, including: concern of pain medication addiction, competing activities, treatment side effects, health status, desire for autonomy, and symptoms of depression. Results of qualitative analyses also revealed the presence of additional factors that could facilitate adherence to treatment recommendations. Taking into consideration findings from both quantitative and qualitative analyses, adherence may be best conceptualized as a result of a dynamic decision-making process influenced by numerous interacting factors. This study is the first to examine barriers to adherence among adolescents following unintentional injury and provides an initial roadmap for understanding the mechanisms involved in this complex process.