OBJECTIVE We studied preoperative and perioperative factors with particular attention to the role of immunomodulatory medication, which may impact the incidence of pouch-related septic complications. METHODS A retrospective review of data from patients who underwent ileal pouch surgery during a 20-year period from 1985 to 2005 was performed. Preoperative use of immunomodulatory medication along with perioperative clinical, surgical, and disease variables were recorded. Patients were monitored for pouch-related sepsis in the early (within 30 days of surgery) and late (after 30 days of surgery) postoperative periods. Univariate and multivariate logistic regression analysis was performed. RESULTS There were 445 patients (206 females; 46.4 percent). Median age was 36 (interquartile range, 27-46) years. Median follow-up period was 52 (interquartile range, 26-86) months. Complete data were available for 335 patients. Early sepsis was seen in 58 patients (17.3 percent). Another 22 patients (6.5 percent) developed late sepsis. On multivariate analysis, only steroid use remained predictive of higher rates of early sepsis (odds ratio, 1.81; 95 percent confidence interval, 1.02-3.45; P=0.002). Likewise on multivariate analysis, both male gender (odds ratio, 0.24; 95 percent confidence interval, 0.09-0.71; P=0.007) and 5-aminosalicylic-acid use (odds ratio, 0.22; 95 percent confidence interval, 0.08-0.76; P=0.023) remained predictive of lower rates of sepsis. CONCLUSIONS Preoperative steroid use is associated with higher rates of early but not late pouch-related septic complications. We recommend that patients be weaned of steroids before ileal pouch surgery or be warned of the higher risk of postoperative sepsis.