Aims. The aim of this investigator-initiated prospective randomized open-label single institutional trial is to evaluate the role of acupuncture in the treatment of acute skin and mucosal toxicity, xerostomia, and perception of taste, pain, and nausea related to curative and adjuvant (chemo)radiotherapy of head and neck cancer. This paper reports pilot data of the first 30 enrolled patients. Methods. Patients were randomized to undergo standard of care radiotherapy +/- chemotherapy and support care defined by our institutional standard operating procedures alone or in the combination with acupuncture which was initiated with the first signs of any toxicity. Results. Fifteen patients were enrolled in both arms and all finished the treatment as planned.The median pain was significantly lower in the acupuncture arm (median 1.6 points vs. 2.5 points on a 10-item Likert scale; P=0.035) as well as duration of acute pain (median 31 days vs. 54 days; P=0.031). Patients with acupuncture had significantly shorter duration of acute skin (median 44 days vs. 109 days; P<0.001) and mucosal toxicity (median 34 days vs. 109 days; P<0.001) with no difference in grading of toxicity (median grade 1.6 vs. 1.5; P=0.701 and median grade 1.4 vs. 1.6; P=0.204 for skin and mucosa, respectively). No significant difference was found for other toxicity domains, with the exception of salivation toxicity which was significantly lower in acupuncture arm (median grade 1.3 vs. 1.7; P=0.048). Conclusion. In this interim analysis, acupuncture leads to lower pain andfaster disappearance of skin and mucosal toxicity after (chemo)radiotherapy of head and neck cancer. Description and validation of acupuncture using scientific approaches will further enhance acceptance of this method by both patients and health care providers.