In 2005, the Siena Saints were picked to finish last in preseason polls for the Metro Atlantic Athletic Conference. However, McCaffery orchestrated the fifth greatest turnaround in all of Division 1 and guided Siena to a 15–13 record. The team earned several memorable victories in the regular season, including an 82–74 win against cross-town rival Albany, and an 82–76 triumph at eventual MAAC champion Iona. The Saints clinched a first-round bye in the MAAC tournament with a 98–92 double-overtime victory over Niagara on the team’s senior day. Siena’s season ended with a 63–62 loss to St. Peter’s in the MAAC quarterfinals.

McCaffery guided Siena to a 20–12 record in 2007. The Saints began the season with an 11–10 record. However, the team went on a late-season winning streak and won 9 of 10 games. Season highlights included a 76–75 double-overtime victory over rival Albany. Siena was one of the youngest teams in the conference with five underclassmen. The Saints reached the 2007 MAAC championship game and lost to Niagara 83–79.

On November 17, 2007, McCaffery guided Siena to a 79–67 victory over #20 ranked Stanford at the Times Union Center in Albany. The win was Siena’s first over a ranked opponent since their first-round victory against the Cardinal in the 1989 NCAA tournament. Siena finished the regular season at 19–10 and 13–5. They tied with Rider for first place in the MAAC. The Saints defeated Manhattan, Loyola and Rider on their way to winning the MAAC championship and an automatic NCAA tournament bid. It was the Siena’s fourth trip to the NCAA Tournament and their first under the guidance of McCaffery. In March 2008, the 13th seeded Saints soundly defeated #4 Vanderbilt 83–62 in the first round of the NCAA Tournament in the Midwest Region. Siena’s season ended one game short of the sweet sixteen in an 84–72 loss to 12th seeded Villanova. Siena finished the season at 23–11. It was the most wins for a Siena team since the 1999–2000 season.

McCaffery was hired by the University of Iowa on March 28, 2010, to replace Todd Lickliter. He was introduced during a press conference and a public ceremony in Carver-Hawkeye Arena on March 29, 2010.

McCaffery lost his first game as head coach at Iowa on November 16, 2010, when the Hawkeyes lost to South Dakota State. His first conference win with the Hawkeyes came against Indiana in Iowa City on January 23. His first win versus a ranked team as the head coach of Iowa came on March 5, when Iowa defeated No. 6 Purdue, 67–65. That win snapped a 25-game losing streak against ranked opponents for the Hawkeyes.

Patrick McCaffery joined his brother Connor by committing to Iowa in 2018. He is considered a top 100 recruit for the class of 2019.