We evaluated whether or not the effect of adalimumab (ADA) in combination with the disease-modifying antirheumatic drugs (DMARDs) other than methotrexate (MTX) is comparable to the ADA+MTX therapy for the treatment of rheumatoid arthritis (RA). A total of 216 patients with active RA at Kohnan Kakogawa Hospital and Kobe University Hospital were enrolled. Clinical and functional outcomes were compared among 4 groups, ADA alone (A group), ADA + MTX (B group), ADA + MTX + other DMARDs (C group), and ADA + other DMARDs (D group), and the retention rates of ADA were evaluated with or without MTX. CRP was significantly decreased from initial measurement at 1 month in all 4 groups, but the continuous efficacy with the statistical significance at all measurement points were observed only in combination with MTX (P<0.05), which was reflected by significantly higher retention rates. Similarly, the disease activities were improved, and particularly the remission rates (DAS28-CRP < 2.3) of A, B and C groups (>42.9%) were higher than that of D group (29.4%) at 2 year. An index of patients' basic activities of daily living, M-HAQ score of A, B and C groups was also better than that of D group. While, looking at the mean changes of M-HAQ from the baseline at 2 years, potential effect of other DMARDs on M-HAQ was also suggested. The results show that ADA + MTX therapy is significantly superior than ADA + other DMARDs in ameliorating RA.