OBJECTIVES: Atopic dermatitis (AD) is a chronic inflammatory itchy skin condition. In a recent Spanish study the estimated prevalence of AD in children between 0 and 14 years old was 8.6%. Topical corticosteroids are currently the favoured treatment for AD. However, their use is limited. Tacrolimus ointment has a demonstrated efficacy in the treatment of moderate and severe AD in children. Twice-weekly maintenance treatment has been approved and the aim of this study was to carry out a cost-effective analysis comparing maintenance with standard reactive treatment with tacrolimus ointment from the perspective of the Spanish NHS. METHODS: An economic model was developed to compare maintenance and standard treatment patients for a period of 12 months. For those patients who discontinued tacrolimus treatment  before 1 year, resource use associated with post-discontinuation treatment was identified through a specially convened Advisory Board with a group of clinical experts. Costs in 2012 euros were assigned to the resources identified. Utility values were also inputted into the model.  Results were expressed in terms of total costs and cost/QALY. RESULTS: For patients with moderate or severe AD, twice-weekly maintenance treatment with tacrolimus ointment was shown to be more effective compared with the standard treatment regimen. In the case of severe AD, maintenance treatment was also less costly compared with standard treatment (939 vs. 1,084€).  For moderate AD, the ICER was 1,981€/QALY which is considerably lower than the acceptable cost-effective threshold (30,000€/QALY).  CONCLUSIONS: Twice-weekly maintenance treatment with tacrolimus ointment compared with standard reactive treatment would appear to be cost-effective and an additional option for clinicians for the treatment of children suffering with moderate and severe AD in Spain.