Midway through her junior year high school she left school to star on the soap opera Another World, playing Marguerite “Maggie” Cory. She then got a role on Nash Bridges, playing Cassidy, the daughter of Don Johnson’s title character. She and her mother moved to Hollywood, so Jodi completed her schooling by mail.
She made her big screen debut in 1998 in Halloween H20: 20 Years Later and later starred in such films as The Crow: Salvation, Whatever It Takes and Devil In The Flesh 2. In 1999, she starred in the teen film She's All That (1999) alongside Freddie Prinze Jr and Rachael Leigh Cook. When asked if it was hard to play her character, a high school prima donna, she replied, “Everybody knew a Taylor Vaughan in high school. Working in show business, you meet girls like that every day.”
O'Keefe kept on filming both movies and Nash Bridges until the series ended in 2001. Later films have been Out For Blood where she played a vampire named Layla Simmons and Venice Underground. In 2005, she appeared for three episodes in the first season of Boston Legal.
O'Keefe was also in 3 Doors Down's video "Let Me Go", alongside Jesse Metcalfe of Desperate Housewives. She joined the cast of Prison Break in 2007.
She appeared in episodes of the television series' Charmed, The Evidence, Two and a Half Men, The Big Bang Theory, Dharma & Greg and Tru Calling. In 2009 she appeared in the video game version of Command & Conquer.
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