In 2006, he published the results of a study conducted from 2003 to 2005 at Allegheny General Hospital along with a team of doctors led by Richard Shannon, in the "Joint Commission Journal on Quality and Patient Safety". It showed reduction in infections through a team coordinating to prevent infections in the bloodstream. He also rejoined PRHI as its CEO in October 2003. O'Neill became a trustee of the University of Pittsburgh Medical Center in February 2003, but left in September 2004 due to it not joining a programme to make hospitals eliminate medical errors. During his tenure he often disagreed with UPMC's CEO Jeffrey Romoff and also opposed its plans to shut Highmark insured patients from receiving treatment at affiliated hospitals in 2019.