In recent years, the concept of “global cardiovascular risk assessment” has grown in interest for its role in primary prevention of cerebro-cardiovascular diseases. Interventions for reducing the risk of relapse for persons with past history of these diseases are well agreed-on. On the contrary, the risk status of persons without such a history varies greatly, and this variability implies a range in the intensity of interventions. In several countries, guidelines for general practitioners have been diffused about pharmaceutical prescriptions in presence of various risk degrees. In particular, in Italy, a governmental drug management commission has established that statins, the most used cholesterol lowering medicines, can be refunded by the National Healthcare System only if prescribed to hyper-cholesterol patients with a global risk greater than 20%. The question is: how to calculate the risk? We performed a review of both the web and the literature and we found a lot of different “risk calculators”. By means of a simulation study, we showed that these tools, when applied to the same person, may lead to very different results. We estimated the economic impact of using one or another calculator.