BACKGROUND: Many preventable diseases such as ischemic heart diseases and breast cancer prevail at a large scale in the general population. Computerized decision support systems are one of the solutions for improving the quality of prevention strategies. METHODS: The system called EsPeR (Personalized Estimate of Risks) combines calculation of several risks with computerisation of guidelines (cardiovascular prevention, screening for breast cancer, colorectal cancer, uterine cervix cancer, and prostate cancer, diagnosis of depression and suicide risk). We present a qualitative evaluation of its ergonomics, as well as it's understanding and acceptance by a group of general practitioners. We organised four focus groups each including 6-11 general practitioners. Physicians worked on several structured clinical scenarios with the help of EsPeR, and three senior investigators leaded structured discussion sessions. RESULTS: The initial sessions identified several ergonomic flaws of the system that were easily corrected. Both clinical scenarios and discussion sessions identified several problems related to the insufficient comprehension (expression of risks, definition of familial history of disease), and difficulty for the physicians to accept some of the recommendations. CONCLUSION: Educational, socio-professional and organisational components (i.e. time constraints for training and use of the EsPeR system during consultation) as well as acceptance of evidence-based decision-making should be taken into account before launching computerised decision support systems, or their application in randomised trials.