Objectives: To evaluate risk factors for serious infections (SI) in Crohn's disease (CD) patients (pts) from the TREAT registry. Methods: TREAT, a prospective registry, was established to study the long-term safety of infliximab(IFX) and other therapies in CD. We evaluated the demographics, disease characteristics, and medication regimens [IFX, prednisone (PRED), immunomodulators (IMM), narcotic analgesics (NARC)] associated with the time to first SI using Cox proportional hazards regression models. Results: 6273 pts were enrolled: 3401 received IFX and 2872 received other therapies only (mean follow-up of 4.8 yrs). In a multivariate model including medication regimens, significant risk of SI was observed for pts with colonic and ileal disease [Hazard Ratio (HR) 1.64; CI (1.21, 2.40) vs colon only] ,moderate/severe disease activity [HR 2.34; CI (1.56, 3.56) vs remission], and years since diagnosis [HR 1.02; CI (1.01, 1.04)]. The table presents HR (CI) and p-value, adjusted for demographics and disease factors. Conclusions: IFX or PRED alone conferred a 2-fold increase risk for SI, whereas NARC increased the risk 6-fold. The highest risk was observed for PRED and NARC together (10-fold) and PRED plus IMM plus NARC (9-fold). SI risk was similar for IFX alone and IFX plus IMM. Disease severity independently conferred a clinically and statistically significant risk for SI. Predictors of Time to First Serious Infection†