Most evaluative research is focused on assessing new technologies at the patient level. Comparatively little is focused on assessing how system changes could improve the delivery of healthcare. In this article, the authors describe an opportunity to conduct evaluative trials of system changes affordably and efficiently by using a cluster randomized design and mandatory reporting data, using the prevention of Clostridium difficile infection as an example. They then describe what must be done to make similar trials a regular tool of healthcare policy.