OBJECTIVES: Poor information on long term outcomes and costs on Tumor Necrosis Factor-α (TNF-α) inhibitors in Psoriatic Arthritis (PsA) are available. Our aim was to evaluate long-term costs, benefits and cost-effectiveness of TNF-α inhibitors in PsA patients with inadequate response to conventional treatment with traditional disease-modifying antirheumatic drugs (DMARDs). METHODS: A total of 55 of the 107 enrolled patients included in the study at one year (Olivieri I et al. Rheumatology,2008;47:1664-70), completed the 5 years follow up period (2005-2010). Patients aged older than 18 years, with different forms of PsA and failure or intolerance to DMARDs therapy were treated with anti-TNF agents. Information on resource use, quality of life, disease activity, function and laboratory values were collected at baseline and through the 5 years of therapy. Costs (expressed in Euro 2011) and utility (measured by EQ-5D instrument) before and after TNF-α inhibitors therapy were compared in order to estimate the incremental cost per quality adjusted life year (QALY) gained. The cost-effectiveness acceptability-curve was also calculated.  RESULTS: Thirty-four patients were males (61.8%), aged mean(SD)= 48.94(11.09) years. The majority of patients (83.6%) had a predominant or exclusive peripheral arthritis. At the end of the 5 years, there was a significant increase in direct costs due to an increase of drug cost caused by TNF-α inhibitors that was partially offset by the decrease in indirect costs. The incremental cost estimated and the utility gained of 0.22 gave an incremental cost-effectiveness ratio of 39,678.6 € per QALY gained for the society. The acceptability curve showed there would be a 90% likelihood that anti-TNF therapy would be considered cost-effective at willingness-to-pay threshold of  €60,000 per QALY gained. CONCLUSIONS: Cost-effectiveness ratios are within the commonly accepted Italian willingness-to-pay threshold. These results show how TNF-α inhibitors could be long-term cost-effectiveness treatment.  Our results need to be confirmed in larger samples of patients.