Background: More than 50% of Department of Veterans Affairs (VA) patients have multimorbidity: the co- occurrence of >2 chronic conditions. Multimorbidity impairs health-related quality of life (HRQoL); leads to psychologic distress, disability, and mortality; and contributes to high health care utilization and costs. Most chronic conditions require patients to engage in disease self-management, including adhering to treatments, making lifestyle changes, and working with their health care team. Patients with multimorbidity face many barriers to self-management and to attending in-person clinic visits. Given the limited time and competing demands of primary care visits, patients with multimorbidity need additional support for self-management. Peer support – assistance provided by non-professionals who are similar to the populations they serve – delivered via telehealth is suited to address these needs. We developed a virtual, Veteran-led peer health coaching intervention, VetASSiST (Veterans Activating Social Support for Self-management and Treatment engagement), to help patients with multimorbidity overcome barriers to self-management and improve HRQoL. Significance: VetASSiST is timely and efficient and aligns with the HSR&D priority that improving care should support coordination and integration of care for the majority of Veterans who have multiple conditions rather than building new single disease interventions. The proposal also aligns with other HSR&D priorities of Primary Care Practice and Management of Complex Chronic Diseases and Virtual Care/Telehealth. Innovation and Impact: Prior peer support trials address individual chronic conditions or mental health. VetASSiST will be one of the first trials of an intervention to support Veterans with multimorbidity. It will also be one of the first to leverage telehealth to remotely deliver peer support, which has the potential to increase access to care. If effective, the intervention could be broadly implemented to improve patient outcomes. Specific Aims: 1) Test the effect of VetASSiST, compared to usual care, on the primary outcome of baseline to 12-month change in physical HRQoL, and secondary outcomes of mental HRQoL and health care utilization; 2a) Describe differences between VetASSiST and usual care on baseline to 12-month changes in intermediate outcomes reflecting the functions of peer support and intervention targets: self-efficacy, patient activation, health behaviors, social support, perceived access to care, patient-provider communication, and shared decision-making; 2b) Examine whether intermediate outcomes mediate intervention-associated differences in HRQoL; 3) Evaluate feasibility of translating VetASSiST into practice, including evaluation of per patient intervention costs and barriers and facilitators to implementation. Methodology: We plan a hybrid type 1 implementation-effectiveness randomized controlled trial of 320 Veterans with complex multimorbidity, defined as >3 chron...