A computerized decision-tree model was used in a cost-comparison study of two ultra-high potency topical corticosteroids (ulobetasol and clobetasol) indicated for the initial treatment of acute attacks of severe localized psoriasis. Among the variable factors involved in this study were the different non-responder rates of the two preparations and the frequencies of the alternative treatments used for non-responders (PUVA, SUP, etretinate or dithranol). National standards for therapeutic procedures of the corticosteroid and alternative treatments used were compiled and assessed from an expert survey. Direct costs (consultations, medication, diagnostics, additional treatments) and indirect health expenditures (loss of productivity) were calculated. Results showed cost-effectiveness advantages for ulobetasol in the range 12–25%. Sensitivity analyses were carried out to test the reliability of these results further. The study revealed that a simple comparison of cost per dose is inadequate to assess fully and understand the socioeconomic dimensions of choices between alternative preparations. The study also underscored the increasing importance of comprehensive socioeconomic evaluations as aids to decision makers in the health-care field.