PROJECT SUMMARY The prevalence of cirrhosis and end-stage liver disease (ESLD) in the U.S. has nearly doubled over the past two decades. Liver transplant (LT) is the only life-saving option for ESLD and is projected to increase 23% by 2040. LT requires considerable healthcare resources, costing the U.S. health system $26.7 billion annually. It is increasingly performed among older adults; from 2006 to 2018, adults 65 and older were the most rapidly growing age group on transplant waitlists. By 2019, 70% of LTRs were adults 50 and older. With advances in immunosuppression (IS) and surgical techniques, average 5-year post-LT survival now exceeds 70%. However, maintaining optimal, long-term liver graft function and overall health are contingent upon proper adherence to prescribed treatment. This can be difficult, as liver transplant recipients (LTRs) contend with high regimen complexity, taking on average 11 new medications that have side effects and require frequent dosage changes. Many LTRs have lingering cognitive impairments due to pre-transplant hepatic encephalopathy, or other psychosocial, financial, or cultural factors that all can affect the ability to adhere to treatment. As a result, a third of LTRs demonstrate inadequate adherence to IS regimens. Poor adherence is a leading cause of liver graft rejection, liver failure, poorly controlled medical comorbidities and subsequent mortality. Similarly, inadequate medication knowledge and unintentional misuse are associated with post-transplant hospitalizations. Despite the negative and costly consequences of inadequate adherence, very few prospective interventions have been developed and tested to optimize medication-taking behaviors and subsequent outcomes post-LT. However, there are unique considerations within the context of LT that can be leveraged by interventions: 1) LTRs remain indefinitely connected to transplant centers for follow-up with a range of available resources; nurse coordinators, pharmacists, psychological and social services; 2) to be eligible for LT, patients must have involved caregivers to provide post-LT support (yet no interventions to date have involved caregivers). Our primary aim is to test the effectiveness of a technology-enabled intervention (TEST trial) to improve treatment adherence and optimize patient-centered and clinical outcomes among a cohort of 360 de novo LTRs at 3 diverse transplant programs in Philadelphia, PA, Chicago, IL, and Miami, FL. Our intervention leverages existing transplant center resources, caregiver support, and widely available patient-centered mobile health tools to remotely monitor LTRs' adherence behaviors, `phenotype' adherence concerns, and tailor transplant center responses to those concerns. We additionally plan to assess intervention fidelity, enabling us to evaluate patient, caregiver, provider and health-system barriers to optimal implementation to enhance scalability. Finally, we will determine the costs and cost-effectiveness ...