Objective To study immunologic mechanisms induced by different TNF-inhibitors in ankylosing spondylitis treatment. Methods A total of 180 patients with ankylosing spondylitis received TNF-α inhibitors were collected. Distribution of different TNF-inhibitors and adverse reactions of patients were observed. Results Three kinds of TNF-inhibitors were used. Among the patients, 50 were treated with Infliximab; 50, with Adalimumab; and 80, with Etanercept. The adverse reaction rates were 14%, 13%, 4%, and 6% in Infliximab, Etanercept (domestic), Etanercept (imported), and Adalimumab, respectively. The humanized TNF-inhibitor was safer than the human-mouse chimeric TNF-inhibitor. Conclusion The human-mouse chimeric TNF-inhibitor was more likely to induce adverse reactions, which might be related to its immunogenicity.