O'Keefe first started his television career in 2003, starring in Channel Seven's AFI-nominated sketch show Big Bite (the same show on which Summer Heights High's Chris Lilley had his TV debut). Late the same year he began hosting Deal or no Deal, the first version of the show outside its home country of the Netherlands. It has been on screen continuously since 2003, has run to over 1,500 episodes to December 2010. In 2005 he hosted the short-lived Dragons Den. In 2010 O'Keefe appeared in the Christmas special episode of Review with Myles Barlow.