OBJECTIVES: The Clinical Decision Support Systems (CDSS) can be intended as tools to improve the health care. The Optimcare Study objectives are to implement a clinical guideline to manage hypercholesterolemic patients on a CDSS and to assess its impact in cost-effectiveness terms, in usual practice conditions. METHODS: Naturalistic and unicentric design in which a therapeutically intervention including a CDSS and a flexible patient education was applied and compared between two periods in a patient cohort. Five hundred hypercholesterolemic patients ( ICD9-CM code = 272.0) were randomiously selected from the Primary Health Care center database (CAP Vila Olímpica, Barcelona, Spain). The CDSS implemented algorithms agreed by the participating physicians, with therapeutical recommendations to achieve cLDL objectives in a cost-effective manner. The compared periods were the year before (PRE) and the year after (POS) the first visit in which physicians could access to the CDSS from their physician desk. The clinical and resources consumption data in PRE were obtained from the center database. The effectiveness was assessed through the therapeutical objective achievement in PRE and POS periods referred to the clinical guideline objectives. The costs were assessed from the social perspective. RESULTS: The therapeutical objective achievement increased an 11.9% (54,2% PRE vs 66.1%POS).While cLDL decreased 10 mg/dl (CI95%-14 to-6). The number of pharmacologically treated patients decreased a 14.6% (76.5% PRE vs 61.9%POS). The patient mean total costs were decreased in POS period [difference = €78.4 (IC95% - 94.7 to -62.1)]. Considering all the visits the adherence to the therapeutical recommendations were a 88.4% while showed a decrease until 72.5% when next visit dates recommendations were considered. CONCLUSIONS: The CDSS given recommendations were accepted by the physician in a high degree and were shown as more cost-effective than the usual care practice.