On 29 March 2007, it was announced that O'Leary would replace Kate Thornton as the new host of ITV's The X Factor for at least two series. On 27 March 2015, O'Leary confirmed that he had quit The X Factor after eight years to pursue other projects. Via his Twitter account, he said:
On 27 November 2007, it was announced that Big Brother: Celebrity Hijack was to be O'Leary's last series of Big Brother, and that he would not return in summer 2008. After seven years, he made his final Big Brother appearance on 28 January 2008.
In March 2007, O'Leary signed a year-long contract with Channel 4 to appear on Hollyoaks. However, this was shortened after a series of disputes on set. Jim Rowe, a series writer at the time, said, "He couldn't follow even the simplest commands. It goes to show how vastly different presenting is to acting". O'Leary hasn't acted since. In 2009, O'Leary presented an episode of The Paul O'Grady Show, standing in for Paul O'Grady.
In 2007, O'Leary was an usher at the wedding of Holly Willoughby. He is a practising Roman Catholic. In an interview with Peter Stanford of the Daily Telegraph in February 2008, he "cheerfully" admitted using contraception while living with his future wife: "I do get it in the neck from some Catholics who say I am a buffet Catholic, picking and choosing the bits I like or don't like."