Objectives To investigate the safety of ofatumumab retreatment in rheumatoid arthritis. Methods Patients with active rheumatoid arthritis participating in two phase III trials (OFA110635 and OFA110634) and a phase II extension trial (OFA111752) received individualised open-label ofatumumab retreatment (700 mg X 2 intravenous infusions two weeks apart) ≥24 weeks following the first course and ≥16 weeks following further courses. Retreatment required evidence of clinical response followed by disease relapse. These studies were prematurely terminated by the sponsor to refocus development on subcutaneous delivery. Due to differences in study designs and populations, data are summarised separately for each study. Results 483 patients (243, 148 and 92 in OFA110635, OFA110634 and OFA111752 respectively) received up to 7 treatment courses of intravenous ofatumumab; cumulative duration of exposure was 463, 182 and 175 patient-years, respectively. Mean time between courses was 17–47 weeks. Ofatumumab induced a profound depletion of peripheral B-lymphocytes. Retreated patients derived benefit based on improvement in DAS28. Adverse events were reported for 93% (226/243), 91% (134/148) and 76% (70/92), serious adverse events for 18% (44/243), 20% (30/148) and 12% (11/92) and serious infections for 3% (8/243), 5% (7/148) and 1% (1/92) of patients in OFA110635, OFA110634 and OFA111752, respectively. The most common adverse events were infusion-related reactions during the first infusion of the first course (48–79%); serious infusion-related reactions were rare (<1% [1/243], 5% [8/148], and 1% [1/92] of patients). Two deaths occurred (fulminant hepatitis B virus infection and interstitial lung disease). Conclusions Ofatumumab was generally well tolerated with no evidence of increased safety risks with multiple retreatments. Serious infections were uncommon and did not increase over time