Objectives: To compare the effectiveness of yoga added to standard care (SC) versus SC only, in women with breast cancer during chemotherapy. Design: A multicenter pragmatic, randomized controlled study. Settings/Location: Three hospitals in the Netherlands. Subjects: Women with stage I-III breast cancer undergoing chemotherapy. Interventions: Women were randomized either to a program based on Dru Yoga, once a week yoga sessions for 12 weeks (N=47), or SC only (N=36). Outcome measures: Primary outcome fatigue (Multidimensional Fatigue Inventory [MFI]; general fatigue) and secondary outcomes fatigue (MFI, Fatigue Quality List [FQL]), quality of life (30-item Quality of Life Questionnaire-C of the European Organization for Research and Treatment of Cancer [EORTC-QLQ-C-30]) and psychological distress (Hospital Anxiety Depression Scale [HADS], Impact of Events Scale [IES]) were measured at baseline (T0), 3 months (T1), and 6 months (T2) and analyzed on observed cases. Other outcomes were adequate relief, reintegration to work, and adverse events. Results: No significant differences were found in general fatigue at T1 (MFI: yoga; 14.64.5 vs. SC; 14.2 +/- 4.2, p=0.987). Similar findings were observed for other fatigue (sub)scales of MFI and FQL and functional domains of EORTC. With respect to EORTCs symptom scales, women in the yoga group reported significantly less nausea and vomiting compared with SC at T2 (p=0.004), but not at T1 (p=0.807). Depressive symptoms were significantly lower with yoga at T1 (HADS: yoga; 4.7 +/- 4.1 vs. SC; 5.1 +/- 4.2, p=0.031). More women in the yoga group experienced adequate relief compared with SC at T1 (yoga; 51% vs. SC; 19%) and had returned to work at T2 (yoga; 53% vs. SC; 23%). No adverse events were reported with yoga. Conclusions: A Dru-based yoga program failed to demonstrate a significant beneficial effect on fatigue. Possible favorable effects of the yoga program on nausea and vomiting and early return to work in breast cancer survivors warrant further research.