With great improvements in survival in patients with locally advanced prostate cancer, quality of life (QOL) is becoming an important factor in the selection of treatment. The aim of this study was to evaluate changes in health-related QOL in patients with locally advanced prostate cancer after intensity-modulated radiotherapy (IMRT) combined with androgen deprivation therapy. Patients were treated with IMRT combined with androgen deprivation. Total dose to the prostate was 68.2 Gy (2.2 Gy per fraction), and patients received 50 mg of oral Casodex once daily and 3.6 mg of subcutaneous Zoladex once every 28 days for 2.5 years. QOL was measured using the Expanded Prostate Cancer Index Composite. The time points were baseline, end of radiotherapy, and 3, 12, 36, 48, and 60 months after radiotherapy. From 2002 to 2007, a total of 87 patients were enrolled. Median follow-up time was 76.8 months. Compared with baseline, all four domain summary scores were decreased to varying degrees. Statistically significant changes in the urinary, bowel, and hormonal domain scores were observed (P < 0.05). The changes in scores for urinary incontinence and dysuria were -13.0 ± 8.3 and -6.12 ± 3.9, respectively (P < 0.05). QOL was decreased in patients with locally advanced prostate cancer after IMRT combined with androgen deprivation therapy in all four primary domains, especially in urinary, bowel, and hormonal domains. Nevertheless, the treatment was well tolerated in most patients during the 5 years of follow-up.