Infliximab (INF), a tumor necrosis factor-alpha (TNF-α) inhibitor, is an effective drug for patients with rheumatoid arthritis (RA). However, some patients receive no clinical benefit, or the agents gradually lose their effect. Five sessions of high-throughput leukocytapheresis (LCAP) were given at a frequency of once a week using a Cellsorba CS-180S to four patients with a reduced response to INF. The clinical response to LCAP was evaluated using the 28-joint disease activity score with C-reactive protein (DAS28-CRP) and with the erythrocyte sedimentation rate (DAS28-ESR). DAS28-CRP decreased significantly from 5.8 ± 0.6 before LCAP to 3.9 ± 0.7 (P = 0.0182) at 1–2 weeks after completion of five sessions of LCAP, and DAS28-ESR decreased significantly from 6.4 ± 0.6 to 4.6 ± 0.5 (P = 0.0267). Moreover, all patients had a moderate response according to the European League Against Rheumatism (EULAR) response criteria. The effect of LCAP continued for at least 6 months after its completion in all patients, with no changes in any of their concomitant drugs, and the effect was maintained for at least 1 year in three of the four patients. These results indicate that LCAP is a useful treatment for RA patients with a reduced response to INF.