Guidelines are often based on a mixture of evidence-based and consensus-based recommendations. It is not straightforward that providing a series of “good” recommendations result in a guideline that is easily applicable, and it is not straightforward that acting according to such recommendations leads to an effective and efficient clinical practice. In this paper we summarize our experience in evaluating both the usability and the impact of a guideline for the acute/subacute stroke management. A computerised version of the guideline has been implemented and linked to the electronic patient record. We collected data on 386 patients. Our analysis highlighted a number of non-compliances. Some of them can be easily justified, while others depend only on physician resistance to behavioural changes and on cultural biases. From our results, health outcomes and costs are related to guideline compliance: a unit increase in the number of non-compliance results in a 7% increase of mortality at six months. Patients treated according to guidelines showed a 13% increase in treatment effectiveness at discharge, and an average cost of 2929 $\euro$ vs 3694 $\euro$ for the others.