In patients with rheumatoid arthritis who had symptomatic knee joints at the start of anti-tumor necrosis factor (TNF) therapy, the relationship between local symptoms and knee joint destruction at 94 weeks was retrospectively investigated. Among the patients with rheumatoid arthritis and received anti-TNF therapy, the 32 patients (52 joints) having swollen and/or tender knee joints were included in this study. Changes of disease activity score in 28 joints based on C-reactive protein (DAS28-CRP) and knee joint destruction using Larsen’s grading system 94 weeks after anti-TNF therapy were evaluated. Furthermore, the differences of the DAS28-CRP, swollen and tender knee joints between the patients who showed progression of joint destruction (Progression group) and those who did not (Non-progression group) were investigated. DAS28-CRP showed time-dependent, favorable results. However, progression of joint destruction was observed in 12 out of 52 joints. DAS28-CRP at 0 and 94 weeks after anti-TNF therapy were not different between Progression and Non-progression groups. However, the rate of swollen knee joints was higher in Progression group from 0 week. In addition, the ratio of swollen and/or tender knee joints was higher in Progression group from 22 to 94 weeks after anti-TNF therapy. The disease activity evaluated using DAS28-CRP was improved by anti-TNF therapy, but residual local symptoms in the knee joints were associated with a high incidence of joint destruction progression. We should treat rheumatoid arthritis patients with consideration for the possibility of joint destruction in the knee joints having residual local symptoms to progress.