Introduction: The efficacy and safety of TNF-α blockers have been demonstrated in lot of clinical trials. The use of TNF-α blockers is associated with a significant improvement in the overall symptoms of patients with inflammatory joint diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA). As a result of their use, the functions of affected joints and the quality of life of patients are improved. In recent years, it has been demonstrated that TNF-α blockers produce drug-induced neutralizing antibodies that reduce the effectiveness of these costly drugs. Objective: To investigate drug-induced neutralizing antibodies to TNF-α blockers in patients with inflammatory joint diseases followed by 24-months. Materials and Methods: 121 (56.8%) patients with PA, 50 (23.5%) patients with AS and 42 (19.7%) patients with PsA, treated with TNF-α blockers, were tested at 0, 6, 12, 24 months for drug-induced neutralizing antibodies. Detection of neutralizing antibodies to adalimumab (Humira) is performed by ELISA method, with Immundiagnostik - TNFα-Blocker-ADA, Antikorper gegen Adalimumab (Humira), Immundiagnostik AG, Stubenwald-Allee 8a, D 64625 Bensheim all requirements of the manufacturer. Determination of neutralizing antibodies to etanercept (Enbrel) were performed by ELISA method, with Immundiagnostik – TNF-α-Blocker-ADA, Antikorper gegen Etanercept (ENBREL), Immundiagnostik AG, Stubenwald-Allee 8a, D 64625 Bensheim, all requirements of the manufacturer. The SPSS v.24 statistical program was used. Results and conclusions: Drug-induced neutralizing antibodies in patients with RA, PsA, AS, treated with adalimumab, occurred in 11.5% of the patients 6th months after beginning of the treatment, at 12th months they were 17.64%, at the end of the second year 24.8 %. Patients treated with etanercept do not have proven neutralizing antibodies 6th months after beginning of the treatment, at the end of the first year they were 7.77%, at the end of the second year 9.63%. There is no significant difference between the number of males and females with drug-induced neutralizing antibodies (p=0.01). The number of patients with neutralizing antibodies to adalimumab and etanercept differ markedly in the 12th and 24th month (p=0.01). We recommend that the investigating of drug-induced neutralizing antibodies to TNF-α blockers have to be done every 12th months as a part of the routine work of rheumatologists.