Objective: To assess safety of biologic disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients following rituximab treatment. Methods: RA patients who participated in an international rituximab clinical trial program were included. Patients who had received ≥1 course of rituximab and withdrew from the treatment phase of the study, entered a safety follow-up (SFU) period, during which additional biologic DMARDs were permitted. Serious infection events (SIEs) were collected. Results: Of 2578 patients, 185 entered SFU and received another biologic DMARD as of November, 2007. The majority (88.6%) of patients had peripheral B-cell depletion at time of initiation of another biologic. Of the 185 patients, 153 had received ≥1 TNF-inhibitor(s). In these 185, 13 SIEs (6.99 events/100 patient-years) occurred following rituximab, but prior to another biologic DMARD, and 10 SIEs (5.49 events/100 patient-years) occurred following another biological DMARD. SIEs were of typical type and severity for RA patients. There were no fatal or opportunistic infections. Conclusions: In this analysis, treatment with a biologic DMARD after rituximab was not associated with an increased rate of serious infection. The size of the sample with limited follow-up restricts definitive conclusions about safety in B-cell depleted patients receiving additional biologic DMARDs.