AbstractThis report first describes the efficiency achieved by a large scale clinical trial (GISSI), which is widely recognized as having made an important contribution to the therapy of AMI, and second emphasizes how a comprehensive research project based upon an innovative clinical trial methodology can influence the attitude and the scientific productivity of a professional community operating within a national health system. To understand the methodology of GISSI, one must appreciate both the cultural and institutional setting in which the first GISSI trial took place as well as the strong economic and scientific expectation surrounding the second GISSI trial.