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UNLABELLED: Background Interventions are needed to alleviate memory difficulty in cancer survivors. We previously showed in a phase III randomized clinical trial that YOCAS(c)(R) yoga-a program that consists of breathing exercises, postures, and meditation-significantly improved sleep quality in cancer survivors. This study assessed the effects of YOCAS(c)(R) on memory and identified relationships between memory and sleep. STUDY DESIGN AND METHODS: Survivors were randomized to standard care (SC) or SC with YOCAS(c)(R) . 328 participants who provided data on the memory difficulty item of the MD Anderson Symptom Inventory are included. Sleep quality was measured using the Pittsburgh Sleep Quality Index. General linear modeling (GLM) determined the group effect of YOCAS(c)(R) on memory difficulty compared with SC. GLM also determined moderation of baseline memory difficulty on postintervention sleep and vice versa. Path modeling assessed the mediating effects of changes in memory difficulty on YOCAS(c)(R) changes in sleep and vice versa. RESULTS: YOCAS(c)(R) significantly reduced memory difficulty at postintervention compared with SC (mean change: yoga=-0.60; SC=-0.16; P<.05). Baseline memory difficulty did not moderate the effects of postintervention sleep quality in YOCAS(c)(R) compared with SC. Baseline sleep quality did moderate the effects of postintervention memory difficulty in YOCAS(c)(R) compared with SC (P<.05). Changes in sleep quality was a significant mediator of reduced memory difficulty in YOCAS(c)(R) compared with SC (P<.05); however, changes in memory difficulty did not significantly mediate improved sleep quality in YOCAS(c)(R) compared with SC. CONCLUSIONS: In this large nationwide trial, YOCAS(c)(R) yoga significantly reduced patient-reported memory difficulty in cancer survivors.