OBJECTIVES: Colorectal cancer is one of the most common forms of cancer in Europe and the USA. The aim of this study was to assess prospectively changes of quality of life after surgery for rectal cancer with a focus on sexuality and gender related differences. METHODS: Since 1998, the EORTC-QLQ-C-30 and a tumor specific ad-hoc module were prospectively administered to patients before surgery, at discharge, 3, 6, 12 and 24 months postoperatively. These data were combined with QoL data from a historical cohort of patients that underwent surgery between 1992 and 1997. Altogether, 819 patients with rectum and sigma carcinoma were included in the analysis, 541 of them provided QoL data for at least 1 time point. Comparisons were made between female and male patients. Due to skewed distributions, non-parametric statistical analyses were performed. A global alpha of p<0.05 was considered significant. RESULTS: In total, 262 female and 279 male patients provided QoL data. Both groups were comparable in terms of age, tumor stage and surgical procedure. In men as well as women most QoL scores dropped significantly below baseline in the early postoperative period. From the third month onwards, global health, emotional and physical functioning improved. Female gender was associated with significantly worse global health and physical functioning and with higher scores on treatment strain and fatigue. Men reported more difficulties with sexuality. These problems tended to remain. CONCLUSIONS: These findings confirm that QoL changes post surgery and is different between men and women. Women appear to be affected by impaired physical functioning and global health. Female gender is associated with significantly higher fatigue levels and increased strain values after surgery. In terms of impaired sexual enjoyment, men are put more under strain than woman. All differences between men and women remain stable in the course of time.