Observational outcome studies represent a valid approach to evaluating comparative treatment effectiveness in real populations. The main objective of outcome research is to underline what works and what does not work in the field of health assistance. In 2004 the Italian Ministry of Health launched the Project "Mattone Misura dell'Outcome" aimed at assessing the introduction of procedures and methods for the systematic evaluation of outcomes in the national health system. A new experience, the PROGRESSI program (PROGRamma ESiti per SIVeAS e LEA), started in 2008 with the aim to further develop the methodologies for outcome evaluation. In this Supplement the final results from four clinical studies named "Sperimentazioni dell'area cardiovascolare del Progetto Mattoni" are presented. These studies started between 2005 and 2007 and their main objectives were to evaluate: --the contribution of information from current informative systems and clinical studies in risk-adjustment methodologies; --the advisability of introducing some clinical items in current informative systems to improve outcome estimates; --the goodness of follow-up procedures from current informative systems; and --the role of disease registries in the validation of comparative evaluation measures. The four studies were designed as voluntary prospective multicentre studies. Results concerning the characteristics of the enrolled populations as well as the risk-adjustment models built using information from current informative systems and/or clinical information are presented. As expected, each study produced specific remarks both in terms of clinical findings and contribution of different informative systems to the risk-adjustment models. In general, models built with information from both current informative systems and clinical information show the best performance. Findings from these analyses will provide the public health system with suitable indications to improve statistical methodologies for outcome estimates.