Context and goals Scientific literature currently lacks evidence of sustained clinical impacts of quality improvement programs. If one excludes self-reported results and initiatives with no institution-wide perspective, one is left with no evidence at all. Our research program therefore targeted positive outliers. With the help of a panel of international experts, we have chosen three leading healthcare systems in quality improvement, to be the subject of in-depth investigation. Program: Description, Implementation and Follow-up The case-study methodology has been applied to three innovative hospital systems: Intermountain Healthcare (USA), Jönköping County Council (Sweden) and Reinier de Graaf (Netherlands). The research combined quantitative and qualitative methods to study the content, the implementation and the results of these improvement programs. During our interviews, we asked our informants if they had witnessed any clinical impacts of the improvement program. If they did, we asked them if they had any data to support their perception. Our study then focused on analysing and cross-checking perception and quantitative data. Results in Terms of Clinical Impact The study shows that quality improvement programs can lead to an impact on clinical outcomes, providing that a set of conditions is satisfied. There is evidence of clinical outcomes improvements in a number of departments in one case and in one single department in another case. There are clinical process improvements in all of the three cases. Discussion The research program highlights the structure and the skills that need to be developed to support sustained clinical improvement in the hospital: for example a culture of improvement, of organisational learning, of evidence-based decision making; the development of clinical leadership; the capacity to keep the focus on improvement during crises; and a clinical information system coupled with clinical indicators that are aligned with the improvement strategy. The study suggests the concept of an ...