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Shoulder pain and disability are well recognized complications associated with surgery for head and neck cancer. This study was designed to examine the effects of progressive resistance exercise training (PRET) on upper extremity pain and dysfunction in postsurgical head and neck cancer survivors.Fifty-two head and neck cancer survivors were assigned randomly to PRET (n = 27) or a standardized therapeutic exercise protocol (TP) (n = 25) for 12 weeks. The primary endpoint was change in patient-rated shoulder pain and disability from baseline to postintervention. Secondary endpoints were upper extremity strength and endurance, range of motion, fatigue, and quality of life.Follow-up assessment for the primary outcome was 92%, and adherence to the supervised PRET and TP programs were 95% and 87%, respectively. On the basis of intention-to-treat analyses, PRET was superior to TP for improving shoulder pain and disability (−9.6; 95% confidence interval [95% CI], −16.4 to −4.5; P = .001), upper extremity strength (+10.8 kg; 95% CI, 5.4–16.2 kg; P < .001), and upper extremity endurance (+194 repetitions × kg; 95% CI, 10–378 repetitions × kg; P = .039). Changes in neck dissection impairment, fatigue, and quality of life favored the PRET group but did not reach statistical significance.The PRET program significantly reduced shoulder pain and disability and improved upper extremity muscular strength and endurance in head and neck cancer survivors who had shoulder dysfunction because of spinal accessory nerve damage. Clinicians should consider the addition of PRET in the rehabilitation of postsurgical head and neck cancer survivors. Cancer 2008. © 2008 American Cancer Society.