The primary objective of this work was to determine the feasibility of a randomized trial of individualized yoga for children receiving intensive chemotherapy and for hematopoietic stem cell transplantation (HSCT) recipients outside of the principal coordinating institution. We evaluated the feasibility of a randomized trial of individualized yoga versus an iPad control program at a site where external yoga instructors were hired and compensated per session. Subjects were children receiving intensive chemotherapy for hematological malignancies and autologous or allogeneic HSCT recipients expected to be hospitalized for 3 weeks. Yoga or iPad control contact occurred daily for 21 days (excluding weekends and holidays); fatigue and quality-of-life outcomes were measured at baseline, day 10, and day 21. Ten eligible subjects were identified; six subjects consented and were enrolled. Three were randomized to the individualized yoga intervention and three to the iPad control program. The median age of participants was 12 (range 8–15) years, and 2 (33%) were boys. Challenges primarily related to the hiring of yoga instructors who were not trained in research methods. We found issues with: (1) logistics of hiring, training, and retaining instructors; (2) communication between teams; (3) fidelity to the protocol and outcome assessments; and (4) ensuring safety. We found that a randomized trial of individualized yoga presented new challenges when relying on externally contracted yoga instructors. Future multicenter studies of yoga should seek to better integrate practitioners within the research team to improve processes, communication, fidelity to the protocol, and safety.