Backgraund/Aims: Recently, some authors have suggested that the development of ulcerative colitis (UC) has a strong negativc association with appendectomy, while others have claimed a weak association. We postulated that this discrepancy might be partly explained by the smoking status, a well-known confounding variable, because the previous studies did not consider the smoking status. This study was carried out to evaluate the relationship between appendectomy and the risk for the development of UC after control of smoking status. METHODS: The 201 patients with UC and 201 controls recruited from the orthopedic-traumatology clinic were included in this study. For the selection of controls, we matched smoking status as well as age (+1 yr) and sex. For all patients and cantrols, data of previous appendectomy were collected. RESULTS: Prior to development of UC, appendectomy had been performed in 3 out of 201 patients with UC (1.5%) and in 27 out of 201 controls (13.4%). The odds ratio for patients with UC, who had received an appendectomy was O. 1 1 (95% CI, 0.03-0.37; p<0.001). CONCLUSIONS: Even after control of the smoking factor, appendectomy is negatively associated with ulcerative colitis.