Background: Up to 50% of breast cancer patients on aromatase inhibitor therapy report significant musculoskeletal symptoms such as joint and muscle pain, which decreases treatment adherence. We conducted a secondary data analysis of a multi-site, phase III randomized, controlled, clinical trial examining the efficacy of yoga for improving musculoskeletal symptoms among breast cancer patients currently receiving hormone therapy (aromatase inhibitors [AI] or tamoxifen [TAM]) through the University of Rochester Cancer Center Community Clinical Oncology Program (CCOP). Methods: The original RCT randomized patients with any type of non-metastatic cancer without previous yoga participation into 2 arms: 1) standard care monitoring [controls] or 2) 4-week yoga intervention (2x/wk; 75 min/session) plus standard care. The yoga intervention utilized the UR Yoga for Cancer Survivors (YOCAS) program consisting of breathing exercises, 18 Hatha and Restorative yoga postures, and meditation. Only breast cancer patients currently receiving AI (N=95) or TAM (N=72) were included in this secondary analysis. Changes in musculoskeletal symptoms were assessed using ANCOVA with baseline values as covariates between the yoga and control groups. Results: Compared to TAM users at baseline, AI users reported higher levels of general pain (1-5 score: AI=2.65 vs. TAM=2.17; p=0.01), muscle aches (0-4 score: AI=2.14 vs. TAM=1.65; p=0.01), and total physical discomfort (0-24: AI=8.03 vs. TAM=5.92; p=0.01). Among AI users only, participants in the yoga group demonstrated greater reductions in general pain (CS=change score; Yoga CS= -0.37 vs. Control CS= +0.02; p=0.02), muscle aches (Yoga CS= -0.58 vs. Control CS= -0.15; p=0.03) and total physical discomfort (Yoga CS= -2.07 vs. Control CS= -0.58; p=0.04) from pre- to post-intervention than the control group. Conclusions: The severity of musculoskeletal symptoms was higher for AI users than for TAM users. Among breast cancer patients on AI therapy, the community-based YOCAS intervention significantly reduced general pain, muscle aches, and physical discomfort. Funding: NCI U10CA37420, KL2RR024136-05, K07CA120025.