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Ankylosing spondylitis (AS) is a chronic immune-mediated disease affecting the sacroiliac joints and the spine, manifesting with new bone formation and osteopenia. Five tumor necrosis factor-alpha (TNF-α) inhibitors (infliximab, etanercept, adalimumab, certolizumab, and golimumab) are available for the treatment of AS, however, the results for the safety of TNF-α inhibitors in the treatment of AS are not consistent.In this study, we conducted a meta-analysis to determine the safety of TNF-α inhibitors compared with placebo in reducing pain, swelling, and inflammation of AS patients. Eight relevant articles including 2049 patients were included for this meta-analysis study. We observed that the incidence of adverse events (RR = 1.22, 95% CI: 1.12–1.33; P = .501, I2 = 0%) and injection-site reaction (RR = 2.93, 95% CI: 2.02–4.23; P = .691, I2 = 0%) in AS patients’ treatment with TNF-α inhibitors was significantly higher than that with placebo.However, there was no significant difference in the incidence of serious adverse event, infection, serious infection, and discontinuations due to adverse event. TNF-α inhibitors may be a promising treatment for AS, but carries an increased incidence rate of adverse events and injection-site reaction.Due to the existence of the unstable factors, further studies need to be done to verify the result of this study.