OBJECTIVES: The introduction of tumor necrosis factor (TNF) inhibitors such as etanercept and infliximab has represented a critical advance in the available treatments for patients with Ankylosing Spondylitis (AS). Several clinical studies have shown superior efficacy of TNF inhibitors, but high costs and infrequent instances of serious adverse side effects ask for priority setting. The aim of this review was to identify and summarize the pharmacoeconomic evidence of TNF inhibitors in AS and to provide a critique of the methodology using Drummond's 10-point checklist. METHODS: A systematic literature search was conducted by one researcher among publications in peer-reviewed journals from January 2000 to April 2006 through electronic databases (Medline, Embase, and Cochrane Database). Only studies that provided economic evaluations of TNF inhibitors in AS were included in the review. RESULTS: The search yielded a total of eight cost studies. Only four met study inclusion criteria. Three of the four studies were cost-effectiveness analysis and two of the four compared etanercept and infliximab in patients with AS. The analytical time frame ranged from one year to 30 years. Costs and effects were appropriately discounted and sensitivity analysis was conducted to test the robustness of the model assumptions. Outcomes were presented as cost per quality-adjusted life years (QALYs) or cost per Assessment in Ankylosing Spondylitis Response Criteria. The incremental cost-utility ratio of etanercept or infliximab varied between US $50,000-$250,000 per QALY when compared with usual care. CONCLUSION: The costs per QALY ratios for the TNF inhibitors seem to be a little higher than the normally accepted societal thresholds ($50000/QALY). The heterogeneity in the cost-effectiveness results could be due to factors like patient demographics, funding source and methodological variables. Nonetheless, TNF inhibitors are a valuable treatment option and further pharmacoeconomic analyses need be conducted to fully evaluate their potential in patients with AS.