The aim of this study was to compare the efficacy and retention rates of three biologics (abatacept, tocilizumab, and etanercept) after switching from first-course anti-TNF monoclonal antibody therapy. We performed a retrospective multicenter study of 89 patients who underwent second-course biologic therapy for 52 weeks after switching from first-course anti-TNF monoclonal antibody therapy. Patients at baseline had a mean age of 58.7 years, mean disease duration of 9.8 years, and mean clinical disease activity index (CDAI) of 22.4. There was no significant difference between the three drugs, except in rheumatoid factor positivity. Retention rates for abatacept, tocilizumab, and etanercept treatment at 52 weeks were 72.0, 89.5 and 84.6 %, respectively. The evaluation of CDAI indicated no significant difference at 52 weeks among the three drugs. Discontinuation due to all unfavorable causes did not significantly differ among the three drugs in hazard ratio-based evaluations. Our results show that patients treated with abatacept, tocilizumab, and etanercept achieved a high response rate with no significant differences in drug retention rates and clinical efficacy. These drugs represent good therapeutic options for patients with RA who are refractory to anti-TNF monoclonal antibody therapy.