We present six cases of patients with Japanese rheumatoid arthritis (RA) treated with a tumor necrosis factor (TNF)-alpha blocking agent, adalimumab as monotherapy for 220 weeks. All six patients were women, and the median age was 54.0 ± 7.07 years old. The median duration of the disease was 7.43 ± 11.1 years, and the median disease activity score (DAS28-CRP) was 5.35 ± 0.69. Three of six patients were able to continue to receive this treatment for 220 weeks successfully, and the DAS28-CRP decreased to 1.89 ± 0.75. Two patients withdrew because of lack of efficacy, and one patient withdrew because of adverse events (non-Hodgkin lymphoma). Adalimumab resulted in a sustained clinical response in RA patients during 220-week follow-up.