Improvement of health-related quality of life (HRQOL) is a major determinant in decision-making for surgery in patients with Crohn's disease (CD). This study was designed to investigate the short- and long-term effect of surgical resection for CD on HRQOL. Sixteen patients were investigated within one week before surgery and 3, 6, and 24 months postoperatively. Besides the Crohn's disease activity index (CDAI), four instruments: the time trade-off technique (TTO), the direct questioning of objectives (DQO), the rating form of inflammatory bowel disease patients concerns (RFIPC), and the Beck depression inventory--were used for assessment of HRQOL. CDAI decreased significantly after operation and 10 patients remained in remission for 24 months. Two patients had postoperative relapses and went into remission after prednisolone treatment. Four patients developed chronic active disease. HRQOL was significantly improved in all patients three and six months postoperatively. Except for the four patients with chronic active disease, all other patients (N = 12) had also significantly improved HRQOL after 24 months. In conclusion, surgical resections in CD lead to a long-term improvement of HRQOL with the exception of patients with chronic active disease. This finding might be taken in consideration for the indication of surgery in CD.