OBJECTIVES: To evaluate whether infliximab, a modern off-label biologic, is cost-effective for treating sarcoid posterior uveitis compared to methotrexate and systemtic steroids.  Sarcoid posterior uveitis is a progressive eye disease that can lead to blindness if untreated.  Ophthalmologists have utilized infliximab, a TNF-alpha inhibitor, which reverses effects of uveitis.  METHODS: A semi-Markov model followed patients’ therapy from the onset of sarcoid posterior uveitis using the societal perspective.  The lifetime model simulated health states that could lead to successful reversal of uveitis with standard or intensified treatment with systemic steroids, methotrexate, or infliximab.  Probabilities, health utilities, and costs were included in the model based on findings from literature.  Costs and effects were discounted at 3% ($US; 2010 values).  We conducted univariate sensitivity analyses, threshold analyses, and a Bayesian multivariate probablistic sensitivity analysis using 10,000 Monte Carlo simulations.  Results were interpretted from a predetermined willingness-to-pay of $50,000/QALY. RESULTS: In order of cost, base case results showed systemic steroids most affordable ($26,871; 14.58 QALYs), followed by methotrexate ($40,351; 15.92 QALYs), and then infliximab ($46,547; 15.04 QALYs).  Methotrexate was cost-effective compared to steroids, with an incremental cost-effectiveness ratio of $10,053/QALY.  Methotrexate dominated infliximab. Univariate sensitivity analyses suggested that the model was sensitive to the utility of a patient’s successful recovery from uveitis (0.84 QALYs). If patients’ health utility after successful recovery is below 0.750, then infliximab has a greater net benefit than methotrexate. The multivariate probabilistic sensitivity analysis showed that methotrexate dominated infliximab in 60% of the simulations. CONCLUSIONS: This cost-effectiveness analysis suggests that despite major advances in the use of biologics for treating sight-threatening sarcoid posterior uveitis, methotrexate remains a less expensive and more cost-effective strategy.  Methotrexate should be adopted as the standard of care for treatment considering its incremental cost-effectiveness at a reasonable willingness-to-pay. Other therapeutic options, such as infliximab, may be considered for certain cases.