BACKGROUND: Patients with locally advanced rectal cancer have a poor prognosis and the early and late postoperative morbidity is high. The aim of this study was to assess health-related quality of life (HRQL) in patients treated with extensive surgical resections for locally advanced rectal cancer and to compare the results with those in patients treated for primarily resectable rectal cancer. METHODS: Between 1991 and 2003, 142 patients with locally advanced rectal cancer had an extensive resection at the Karolinska Hospital in Stockholm, Sweden. A HRQL assessment with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-CR38 questionnaires was performed in patients alive and disease free in 2005. The results were compared with an age- and sex-matched reference group of patients with primarily resectable rectal cancer having had total mesorectal excision alone. RESULTS: The study group of 43 patients (81% of eligible) scored clinically and statistically significantly lower in global quality of life, role function, physical function, social function, and body image and reported a higher degree of pain and fatigue compared with the reference group of 80 patients. In the study group, men scored lower than women in global quality of life, role functioning and social functioning and reported more problems with fatigue. CONCLUSION: Several aspects of HRQL are impaired in disease-free patients treated for locally advanced rectal cancer. This knowledge may be useful in the preoperative counselling and postoperative support of these patients.