ABSTRACT For many patients with advanced lung disease, lung transplantation is the last viable treatment option to improve their quality of life (QoL) and extend their survival. With the growing number of individuals suffering from end-stage lung diseases, the frequency of lung transplantation has increased exponentially over the past two decades; more than 2,500 patients have been transplanted in the United States in 2016, a number that is expected to increase in the coming years. Despite advances in surgical techniques and medical management, median long term survival has plateaued at about 6 years, and, surprisingly, mental health QoL may not improve significantly after transplant. Developing treatments to extend life and improve QoL among individuals with advanced lung disease is a public health priority. Low functional capacity, physical inactivity, and heightened emotional distress are common following lung transplantation and are associated with increased risk of mortality and re-hospitalizations. Therefore we hypothesize that improving psychological well-being and functional capacity will further translate into improved QoL and better medical outcomes among lung transplant recipients. Prior research has shown that coping skills training (CST), designed both to teach patients self- management skills and to cope more effectively with psychological stress associated with chronic illness, is effective for a number of chronic conditions including diabetes, ischemic heart disease, arthritis, and heart failure. However, CST has not yet been evaluated as an intervention to facilitate self-management of lung transplant recipients, an even more complex condition in which patient self-management, regular exercise, and medication adherence are critical to successful outcomes. We propose a randomized clinical trial comparing a 12-week combined coping skills training and exercise (CSTEX) intervention with standard of care plus transplant education (SOC-ED) in a study sample of 150 lung transplant outpatients recruited from Duke University Medical Center and Washington University School of Medicine. The proposed CSTEX intervention, delivered by respiratory therapists using mHealth technology, is designed to reduce distress and depression and to improve key health behaviors, including physical activity, monitoring of pulmonary function, and adherence to medication, which have been shown to be related to medical outcomes in transplant recipients. Before and following treatment, overall distress and QoL indicated by both physical and mental health functioning, will be assessed. Effects of CSTEX on clinical outcomes also will be evaluated over a median follow-up period of 2.5 years. Findings from this trial could lead to the incorporation of coping skills training and exercise promotion into routine self-management interventions as cost-effective approaches to enhance disease management, QoL and medical outcomes in lung transplant patients and provide a basis for extending studies to other populations of patients with advanced lung disease.