This study retrospectively evaluated 288 patients who had undergone ileal pouch-anal anastomosis to determine the incidence of perineal complications and to relate these findings to the pathologic diagnosis, with the goal of specifically clarifying the appropriate surgical management of patients with indeterminate colitis. Of these 288 patients, 235 patients (82 percent) had a diagnosis of chronic ulcerative colitis, 18 patients (6 percent) had indeterminate colitis, 6 patients (2 percent) had Crohn's disease, and 29 patients (10 percent) had familial polyposis. All complications occurred at least 6 months after closure of the stoma and required operative therapy. Of 18 patients with indeterminate colitis, 9 patients experienced complications (50 percent) vs. 8 of 235 patients with chronic ulcerative colitis (3 percent), a highly significant difference (P less 0.001). Furthermore, the risk of eventual ileostomy because of perineal complications was 0.4 percent in patients with chronic ulcerative colitis vs. 28 percent in patients with indeterminate colitis (P less than 0.001). We conclude that a diagnosis of indeterminate colitis predisposes the patient undergoing ileal pouch-anal anastomosis to perineal complications, with a resultant high chance of reservoir loss. Ileal pouch-anal anastomosis should be considered with caution in the patient with a diagnosis of indeterminate colitis.