BACKGROUND: Cancer-related fatigue afflicts up to 33% of breast cancer survivors, yet there are no empirically validated treatments for this symptom. METHODS: The authors conducted a 2-group randomized controlled trial to determine the feasibility and efficacy of an Iyengar yoga intervention for breast cancer survivors with persistent post-treatment fatigue. Participants were breast cancer survivors who had completed cancer treatments (other than endocrine therapy) at least 6 months before enrollment, reported significant cancer-related fatigue, and had no other medical conditions that would account for fatigue symptoms or interfere with yoga practice. Block randomization was used to assign participants to a 12-week, Iyengar-based yoga intervention or to 12 weeks of health education (control). The primary outcome was change in fatigue measured at baseline, immediately post-treatment, and 3 months after treatment completion. Additional outcomes included changes in vigor, depressive symptoms, sleep, perceived stress, and physical performance. Intent-to-treat analyses were conducted with all randomized participants using linear mixed models. RESULTS: Thirty-one women were randomly assigned to yoga (n = 16) or health education (n = 15). Fatigue severity declined significantly from baseline to post-treatment and over a 3-month follow-up in the yoga group relative to controls (P = .032). In addition, the yoga group had significant increases in vigor relative to controls (P = .011). Both groups had positive changes in depressive symptoms and perceived stress (P < .05). No significant changes in sleep or physical performance were observed. CONCLUSIONS: A targeted yoga intervention led to significant improvements in fatigue and vigor among breast cancer survivors with persistent fatigue symptoms. Cancer 2012. (C) 2011 American Cancer Society.