The purpose of this study was to determine the feasibility of an acupuncture clinical trial to prevent radiation therapy (RT)-induced fatigue. We conducted a cross-sectional survey study and a single-arm acupuncture clinical trial among patients undergoing RT. Patients with a Karnofsky score of less than 60, severe anemia, or substantial psychological diagnoses were excluded. Patients received up to 12 treatments of acupuncture over the entire course of their RT. The Lee Fatigue Scale (LFS) was administered at baseline, in the middle of RT, and at the end of RT, along with the Patient Global Impression of Change (PGIC). Among the 48 of 53 (91% response rate) survey participants, 20 (42%) reported that they would participate if the study were available, 13 (27%) would not participate, and 15 (31%) were unsure. Among the 16 trial participants, average fatigue and energy domains of the LFS remained stable during and after RT, without any expected statistical decline owing to RT. Based on the PGIC at the end of RT, 2 subjects (13%) reported their fatigue as worse, 8 (50%) as stable, and 6 (37%) as better. Acupuncture has the potential to prevent RT-related fatigue, which will need to be confirmed by conducting a randomized controlled trial.