Background The purpose of this study was to determine the feasibility of a randomized trial of resistance exercise in patients with head and neck cancer receiving radiation. Methods Fifteen patients with head and neck cancer receiving radiation were randomized to resistance exercise (using resistance bands) or control group. Resistance exercise occurred at the radiation therapy site (weeks 1-6) and home (weeks 7-12). Results No serious adverse events occurred related to resistance exercise. Medium to large effect size differences favoring resistance exercise versus control group were noted for perceived fatigue at 6 weeks (smaller increase in fatigue for resistance exercise group; 7.4 vs 15.4, effect size [d] = -0.64), quality of life at 6 weeks (-7.0 vs -14.4, d = 0.52), and chair rise time (seconds) at 6 and 12 weeks (-1.6 vs 0.4, d = -.63 and -1.9 vs 0.1, d = -0.60, respectively). Conclusions Resistance exercise is safe and feasible in patients with head and neck cancer receiving radiation; a definitive trial is warranted. Copyright © 2012 Wiley Periodicals, Inc.