BACKGROUND: Mind-body practices such as yoga have been studied for their generally positive effects on health-related quality of life (HRQOL). The association between how a person practices yoga and the person's HRQOL is not known. MATERIALS AND METHODS: Yoga practitioners were sent invitations to participate in an online survey via email. Yoga characteristics, HRQOL, and other sociodemographics were collected. Analyses of data from 309 consenting responders evaluated associations between yoga practice characteristics (use of yoga tools, length of practice, location, method, etc.) and the 10-item PROMIS Global Health scale for both physical and mental health components. RESULTS: Multivariable regression models demonstrated higher mental health scores were associated with regular meditation practice, higher income, and the method of practicing in a community group class (versus one-on-one). Higher physical health scores were associated with length of lifetime practice, teacher status, Krishnamacharya yoga style, and practicing in a yoga school/studio (versus at home). CONCLUSIONS: Meditation practice in yoga is positively associated with mental health. Length of lifetime yoga practice was significantly associated with better physical health, suggesting yoga has a potential cumulative benefit over time. Different locations and methods of practice may be associated with varying effects on health outcomes. Comparative cross-sectional and longitudinal studies on the variations in yoga practice are needed to further characterize health benefits of yoga.