In 2009, Oakland announced that DeFrancesco would return to the Sacramento River Cats as manager, replacing Todd Steverson.

[7] On November 30, 2010, the Athletics announced that Darren Bush would replace DeFrancesco as manager of the River Cats.

[10] On August 19, 2012, the Astros announced DeFrancesco would be the interim manager of the major league team for the remainder of the 2012 season, replacing Brad Mills.

[12] With his appointment late in the 2012 season, DeFrancesco served as the final manager of the Astros as a National League franchise.

Tony DeFrancesco then won Baseball America Minor League Manager of the Year Award.

DeFrancesco was named manager of the AAA Las Vegas 51s of the New York Mets organization for the 2018 season.