Objective: Patients with low natural killer (NK) cell activity were shown to have a higher risk of cancer development. Increased cancer risk in rheumatoid arthritis (RA) patients treated with anti-tumor necrosis factor (anti-TNF) agents is still being debated. Therefore, we think it is important to show whether anti-TNF therapy has any effects on the NK cell cytotoxicity in these patients. Material and Methods: We included 60 rheumatoid arthritis patients, 31 treated with anti-TNF therapy, 29 treated with other disease modifying antirheumatic drugs (DMARDs), and 51 ankylosing spondylitis (AS) patients, 35 treated with anti-TNF therapy and 16 treated with nonsteroidal anti-inflammatory drugs or conventional DMARDs as a disease control into the study. The results of two healthy control groups each consisting of 32 age- and. sex- matched healthy individuals were also included. Results: Median values of NK cytoxicity in patients with RA who were being treated with anti-TNF and patients treated with other DMARDs were 29% and 43%, respectively (p=0.203). When we reanalyzed the results independent of clinical diagnosis, patients using anti-TNF medications and patients treated with other medicine had NK cytotoxicity median values of 32% and 43%, respectively (p=0.277). Conclusion: We suppose that NK cell cytotoxicity may decrease in patients with RA when they use anti-TNF agents, and this may help partly to explain why these patients are more prone to development of cancer and severe infections. We think that this study will encourage new studies with higher number of patients to better clarify effects of anti-TNF treatment on NK cell functions.