The aim of this study was to investigate the prevalence of antidrug antibodies (ADAs) against tumour necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). ADAs were detected in 18 (9.8%) patients with RA and in 18 (10.2%) patients with AS of the 360 patients. Development of ADAs was significantly associated with treatment failure in RA patients (P = 0.003). When classified by drugs, the prevalence of immunogenicity in descending order was 17 (28.8%) patients treated with infliximab, 17 (10.4%) with adalimumab, and 2 (1.4%) with etanercept. After adjustment for disease and duration of anti-TNF therapy, the odds ratio as a reference of adalimumab-treated patients was 9.159 (95% confidence interval [CI] 2.005–41.845) for infliximab and 0.280 (95% CI 0.128–0.611) for etanercept. The immunogenicity of anti-TNF therapy was highest in the infliximab-treated group and significantly lower in the etanercept-treated group.