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<p>Little attention has been paid to the psychological determinants by which benefits are accrued via yoga practice in cancer-related clinical settings. Using a longitudinal multilevel modeling approach, associations between affect, mindfulness, and patient-reported mental health outcomes, including mood disturbance, stress symptoms, and health-related quality of life (HRQL), were examined in an existing seven-week yoga program for cancer survivors. Participants (N = 66) were assessed before and after the yoga program and at three- and six-month follow-ups. Decreases in mood disturbance and stress symptoms and improvements in HRQL were observed upon program completion. Improvements in mood disturbance and stress symptoms were maintained at the three- and six-month follow-ups. HRQL exhibited further improvement at the three-month follow-up, which was maintained at the six-month follow-up. Improvements in measures of well-being were predicted by initial positive yoga beliefs and concurrently assessed affective and mindfulness predictor variables. Previous yoga experience, affect, mindfulness, and HRQL were related to yoga practice maintenance over the course of the study.</p>