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OBJECTIVE: The aim of this trial was to evaluate the effects of yoga on health-related quality of life in patients with colorectal cancer.METHODS: Patients with non-metastatic colorectal cancer were randomly assigned to a 10-week yoga intervention (90 min once weekly) or a waitlist control group. Primary outcome measure was disease-specific quality of life (Functional Assessment of Cancer Therapy - Colorectal [FACT-C]) at week 10. Secondary outcome measures included FACT-C subscales: spiritual well-being (FACT - Spirituality); fatigue (FACT - Fatigue); sleep disturbances (Pittsburgh Sleep Quality Inventory); depression and anxiety (Hospital Anxiety and Depression Scale); body awareness (Scale of Body Connection); and body-efficacy expectations (Body-Efficacy Expectations Scale). Outcomes were assessed at week 10 and week 22 after randomization. RESULTS: Fifty-four patients (mean age 68.3 ± 9.7 years) were randomized to yoga (n = 27; attrition rate 22.2%) and control group (n = 27; attrition rate 18.5%). Patients in the yoga group attended a mean of 5.3 ± 4.0 yoga classes. No significant group differences for the FACT-C total score were found. Group differences were found for emotional well-being at week 22 (∆ = 1.59; 95% CI = 0.27,2.90; p = 0.019), sleep disturbances at week 22 (∆ = -1.08; 95% CI = -2.13, -0.03; p = 0.043), anxiety at week 10 (∆ = -1.14; 95% CI = -2.20, -0.09; p = 0.043), and depression at week 10 (∆ = -1.34; 95% CI = -2.61, -0.8; p = 0.038). No serious adverse events occurred in the yoga group, while liver metastases were diagnosed in one patient in the control group. CONCLUSION: This randomized trial found no effects of yoga on health-related quality of life in patients with colorectal cancer. Given the high attrition rate and low intervention adherence, no definite conclusions can be drawn from this trial.