PURPOSE: Infliximab, a chimeric monoclonal anti-TNFalpha antibody, has been found to increase the risk of serious infections compared with the TNF receptor fusion protein etanercept in some studies. It is unclear whether the risk varies by patient characteristics. We conducted a study to address this question. METHODS: We identified members of Kaiser Permanente Northern California who initiated infliximab (n = 793) or etanercept (n = 2692) in 1997-2007. Using a Cox model, we estimated the propensity-score-adjusted hazard ratio (HR) and 95% confidence interval (CI) of serious infections requiring hospitalization or opportunistic infections comparing infliximab initiators to etanercept initiators. We tested whether the adjusted HR differed by age, sex, race/ethnicity, body mass index, and smoking status. RESULTS: The crude incidence rate of serious infections per 100 person-years was 5.4 (95%CI: 3.8, 7.5) in patients <65 years and 16.0 (95%CI: 10.4, 23.4) in patients >/=65 years during the first 3 months following treatment initiation. Compared with etanercept, the adjusted HR during this period was elevated for infliximab in patients <65 years (HR: 3.01; 95%CI: 1.49, 6.07), but not in those >/=65 years (HR 0.94; 95%CI: 0.41, 2.13). Findings did not suggest that the HR varied by the other patient characteristics examined. CONCLUSIONS: An increased risk of serious infections associated with infliximab relative to etanercept did not appear to be modified by patients’ sex, race/ethnicity, body mass index, or smoking status. There was an indication that the increased risk might be limited to patients <65 years. Additional studies are warranted to verify or refute this finding. Copyright (c) 2012 John Wiley & Sons, Ltd.