BACKGROUND: Chronic diseases, including heart disease, stroke, cancer, and chronic pulmonary disease are the leading causes of death and disability worldwide. Compounding symptoms and loss of function, people living with chronic disease often experience reduced quality of life (QoL). Various physical and mental practices have been shown to relieve stress and improve QoL. Yoga is a physical and mental practice that may be a viable approach for improving QoL in people with chronic disease. OBJECTIVE: The objective of this study was to examine and summarize the evidence for the effectiveness of yoga on QoL in patients with chronic disease. DESIGN: The study design was a a systematic review with qualitative synthesis. METHODS: We included randomized controlled trials that evaluated the effect of yoga on QoL or health-related QoL (HRQoL) for individuals with chronic disease. We included only studies that used at least 1 previously validated measure of QoL or HRQoL and specified a minimum duration of follow-up of at least 1 wk. INTERVENTIONS: We included both movement-based and breath-based yoga practices. Studies that included yoga as part of a larger intervention program (eg, mindfulness-based stress reduction training) or studies that did not provide findings specific to yoga were excluded. PRIMARY OUTCOME MEASURES: The primary outcome analyzed was improvement in QoL as measured by a validated QoL or HRQoL scale. RESULTS: Among the 1488 studies that were identified on initial search, 7 articles met all inclusion criteria. Five studies reported a statistically significant advantage over usual care alone for improvement of QoL in patients with chronic disease, but the clinical significance of the differences was clear in only 1 trial. We found considerable heterogeneity among the included studies and study quality was generally low. CONCLUSIONS: More high-quality research is needed to determine the value of yoga as an adjunctive approach to improving QoL in patients with chronic disease.