Since its inception approximately 15 years ago, the ISAResearch group has completed more than 40 randomized controlled trials (RCT) in the field of interventional cardiology, including more than 40,000 patients. Three main principles have characterized the ISAR trials: first, simplicity: 1 question 1 answer; second, a focus on issues that are relevant for practice at the given moment and third, a strong spirit of performing industry-independent studies. The seamless integration of clinical trials into everyday practice and a stringent study discipline allowed inclusion of more than 90% of the patients in 1 of the device or drug trials, the prerequisite for fast recruitment and evaluation of an all-comers population. Moreover, the early setup and maintenance of a comprehensive database with routine follow-up of all patients undergoing percutaneous coronary intervention made it possible to build up a large registry to answer questions beyond clinical trials. Finally, the close collaboration with basic research working groups within the department has triggered new innovations and facilitated translational research from bench to bedside.