Background: The aim was to assess the influence of long-term treatment with tumor necrosis factor alpha (TNF-a) inhibitors on total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and atherogenic index (AI) in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) patients. Methods: A retrospective cohort study was conducted on RA, PsA, and AS patients treated with TNF-a inhibitors for at least 270 days between 2001 and 2011. Levels of TC, TG, LDL, and HDL and the AI were compared with baseline values at 0-6, 6-12, 12-18, and 18-24 months. Patients were further subdivided into three groups according to their HMG CoA reductase inhibitor (statin) treatment status in order to assess their effect on the results. Results: The records of 311 patients (152 RA, 90 PsA, and 69 AS) were reviewed. TC and TG increased following treatment with TNF-a inhibitors, from 180.85 +/- 2.12 mg/dl and 116.00 +/- 3.55 mg/dl at baseline to 188.12 +/- 2.35 mg/dl (p = 0.02) and 132.02 +/- 4.63 mg/dl at 0-6 months (p < 0.01), respectively, and to 184.88 +/- 2.09 mg/dl (p = 0.02) and 129. 36 +/- 4.32 mg/dl at 18-24 months (p < 0.01), respectively. AI increased following treatment with TNF-a inhibitors, from - 0.032 +/- 0.017 at baseline to 0.004 +/- 0.019 at 18-24 months (p < 0.01). LDL decreased significantly in patients who were treated with statins before and during the entire study period, from 119.97 +/- 2.86 mg/dl at baseline to 104.02 +/- 3.57 mg/dl at 18-24 months (p < 0.01), in contrast to an increase in LDL values in patients who did not receive statins during the study. Conclusions: TNF-a inhibitor treatment was associated with a significant increase in TC and TG levels and the AI. Adding statins to the treatment was associated with a significant decrease in LDL levels.