A significant factor in recruitment for participants and conduct of clinical trials is Principal Investigator / Site motivation. A motivated investigator can motivate study staff and increase recruitment potential for a trial and decrease site related issues. Conversely, an Investigator or clinical trial site that is not motivated or loses motivation during a trial can result in recruitment slowing or completely halting. It is not uncommon for sites to silently quit studies they were once excited about. This series of articles will examine the 4 I’s of Investigator / site motivation and unpack what can be done to optimize clinical trial conditions.