OBJECTIVE: To estimate the cost-efficacy of infliximab and etanercept compared to placebo in patients with ankylosing spondylitis (AS). METHODS: Infliximab and etanercept significantly improve signs and symptoms of AS. We analyzed their cost-efficacy based on incremental benefit versus placebo in their respective AS pivotal trials. Inclusion and exclusion criteria were similar for both trials except for permitted concomitant medications. The base model estimates cost efficacy for maintenance therapy, compared to placebo. Costs were estimated based on average dose for a patient receiving maintenance therapy over a 1-year period. The average number of infliximab vials per dose (4) and total doses/year per patient (8) were obtained from ASSERT trial data. Etanercept was assumed to be administered at 25 mg/dose twice weekly. The ASAS 20, ASAS partial remission, DCART 20 response rates, and percent improvement in BASFI at week 24 were used as efficacy measures. RESULTS: In the infliximab trial, 201 patients received infliximab (5mg/kg) and 78 patients received placebo. In the etanercept trial, 138 patients were treated with etanercept 25 mg twice weekly and 139 received placebo. The cost per responder for infliximab as measured by ASAS 20, ASAS partial response, and DCART 20 was $44,790, $89,156, and $54,057, respectively. The corresponding costs per responder for etanercept were $43,271, $116,500, and $58,250. The mean percent improvement in BASFI in the infliximab and placebo arms were 38.5% and 0.1% respectively, leading to a cost per percent BASFI improvement of $490. The corresponding numbers for etanercept were 30% and 2%, leading to a cost per percent BASFI improvement of $541. CONCLUSIONS: The cost-efficacy ratios of infliximab and etanercept maintenance therapies compared to placebo were similar. The cost-effectiveness in clinical practice will depend on the actual dose and effectiveness achieved. Incremental cost-effective comparisons cannot be reliably estimated without a head-to-head trial.