© 2016, American College of Rheumatology. Objective The risks of hospitalized infection associated with biologic agents used to treat rheumatoid arthritis (RA) are unclear. The aim of this study was to determine whether the associated risk of hospitalized infections differed between specific biologic agents used to treat RA. Methods In a retrospective cohort study using Medicare data from 2006-2011 for all enrolled patients with RA, new episodes of treatment with etanercept, adalimumab, certolizumab, golimumab, infliximab, abatacept, rituximab, and tocilizumab were identified. Patients were required to have received another biologic agent previously and to have been continuously enrolled in Medicare medical and pharmacy plans during the baseline period and throughout followup. Followup started on the date of initiation of treatment with the new biologic agent (after previous treatment with a different biologic agent) and ended on the date of the earliest hospitalized infection, at 12 months, after an exposure gap of >30 days, or at the time of death or loss of Medicare coverage. Cox regression analysis was used to calculate the adjusted hazard ratio (HR) for hospitalized infection, adjusting for an infection risk score and other confounders. Results Of 31,801 new biologic treatment episodes in patients who had previously received another biologic agent, 12.0% were with etanercept, 15.2% with adalimumab, 5.9% with certolizumab, 4.4% with golimumab, 12.4% with infliximab, 28.9% with abatacept, 14.8% with rituximab, and 6.3% with tocilizumab. During followup, we identified 2,530 hospitalized infections; incidence rates ranged from 13.1 per 100 person-years (abatacept) to 18.7 per 100 person-years (rituximab). After adjustment, etanercept (HR 1.24, 95% confidence interval [95% CI] 1.07-1.45), infliximab (HR 1.39, 95% CI 1.21-1.60), and rituximab (HR 1.36, 95% CI 1.21-1.53) had significantly higher HRs for hospitalized infection compared with abatacept. Conclusion In RA patients with prior exposure to a biologic agent, exposure to etanercept, infliximab, or rituximab was associated with a greater 1-year risk of hospitalized infection compared with the risk associated with exposure to abatacept.