Background & Aims There are few data on risk of travel for patients with inflammatory bowel disease (IBD). We assessed rates of illness while traveling among patients with IBD. Methods We performed a retrospective, case-controlled study of illnesses among 222 patients with IBD and 224 healthy individuals (controls) during 1099 total trips. Data were retrieved by structured questionnaires, personal interviews, and chart review. Results Participants had 142 episodes of illness during the trips; 92% were enteric disease. An episode of illness occurred during 79/523 (15.1%) trips made by patients with IBD compared with 63/576 (10.9%) trips made by controls (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.01–2.0; P = .04). However, this difference was mostly attributable to the increased incidence of illness among IBD patients traveling in industrialized countries. In contrast, the rate of illness among travelers to developing countries was similar among patients with IBD and controls (34/200, 17% vs 52/243, 21% of trips, respectively; P = .24). Moreover, numerically more controls that traveled to the tropics developed illness than travelers with IBD (43/135 vs 23/97, respectively; P = .18). In multivariate analysis, factors that increased risk for travel illness included frequent flares of IBD (OR, 1.9; 95% CI, 1.1–3.4; P = .02) and prior IBD-related hospitalizations (OR, 3.5; 95% CI, 1.3–9.3; P = .01); remission within 3 months before traveling reduced the risk for illness (OR, 0.3; 95% CI, 0.16–0.5; P < .001). Use of immunomodulatory drugs was not independently associated with risk of illness during travel. Conclusions Patients with IBD have a higher rate of illness compared with controls during trips to industrialized countries, but not to developing or tropical regions. These findings indicate that most travel-associated illnesses stem from sporadic IBD flares rather than increased susceptibility to enteric infections.