Background: Older cancer survivors consistently express the need for interventions to reduce fatigue and maintain quality of life (QOL). We previously showed that yoga, compared to standard care, effectively improved fatigue and QOL among older survivors. Whether yoga is superior to a rigorous behavioral placebo for improving fatigue and QOL in older survivors is unknown. To examine the efficacy of yoga vs a behavioral placebo for improving fatigue and QOL in older survivors. Methods: Older cancer survivors (age 60+) 2-60 months post-treatment were randomized to receive Yoga for Cancer Survivors (YOCAS; 75-minute sessions 2x/week for 4 weeks) or a behavioral placebo (Survivorship Health Education – SHE; 75-minute sessions 2x/week for 4 weeks). The YOCASintervention includes breathing exercises, yoga poses, and mindfulness activities. The SHEplacebo includes education based on ASCO cancer survivorship recommendations. Fatigue and QOL (i.e., overall, physical, emotional, and functional) were assessed pre- and post-intervention with the Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F). The within-group and between-group intervention effects on fatigue were examined by 2-tailed t tests and ANCOVAs. Results: 173 older survivors were enrolled (91% women, mean age 67 [range=60-85], 90% White, 10% racial minority, 2.3% Hispanic, 71% breast cancer). On average, participants completed 6 in-person yoga sessions and 1 additional weekly, home-based yoga practice, for an average of 183 minutes of yoga/week with no intervention-related adverse events. There were significant between group differences on fatigue, where yoga participants reported significantly more improvement in fatigue than controls (1.6±0.9, p<0.05). There were also significant between group differences on the emotional component of QOL, where yoga participants reported significant improvement in the emotional component of QOL but controls did not (0.8±0.4, p<0.045). Moreover, there were statistical trends for between group differences on the physical and functional component of QOL, where yoga participants reported improvements in the physical (0.8±0.4, p<0.063) and functional components of QOL (0.9±0.5, p<0.089) but controls did not. There were significant between group differences on overall QOL, where yoga participants reported significant improvement in overall QOL but controls did not (3.8±1.4, p<0.007). 94% of participants reported the intervention useful for symptom management and would recommend it to others. Conclusions: Results suggest that older survivors: 1) can safely utilize yoga for treating side effects, 2) experience improvements in fatigue and QOL via yoga therapy, and 3) find yoga a useful treatment for side effects and recommend it to others. Future research is needed to confirm these results and increase uptake by older, and ethnically and racially diverse survivors. Clinical trial information: NCT02613364.