To determine whether an association exists between relapse in inflammatory bowel disease and use of nonsteroidal anti-inflammatory drugs (NSAIDs), a retrospective records review was conducted of patients with Crohn's disease, ulcerative colitis, or indeterminate colitis examined at an outpatient tertiary care center between July 17, 2000, and November 1, 2001. Extracted data collected during the patient's last visit included medication use, maintenance therapy, disease activity, and smoking status. Use of NSAIDs was defined as a daily dose or more of any type the month before relapse. Of 60 patients (22, relapse; 38, remission), 9 (41%) in relapse and 10 (26%) in remission used NSAIDs. Maintenance therapy varied from 68% (relapse) to 92% (remission). The adjusted odds ratio between medication use and relapse was 6.31 (95% confidence interval, 1.16-34.38; P = .03). Use of NSAIDs was associated with relapse. A prospective cohort study that corrects for maintenance therapy is needed to evaluate this relationship.