Vardalos had done many different works but gained almost overnight success with her movie My Big Fat Greek Wedding. The success of the movie led to an unsuccessful T.V. series on CBS, called My Big Fat Greek Life. Except for John Corbett, this series featured the original movie cast. In 2004 she followed it up with Connie and Carla, which co-starred Toni Collette. Vardalos and her husband have appeared together in both of those films, as well as Meet Prince Charming (1999). Vardalos also guest starred on The Drew Carey Show in 1997, where Gomez was a frequent guest star. As of 2007, her next works are the movies A Wilderness of Monkeys and My Life in Ruins, which will arrive in theaters in 2008.

Vardalos was featured in The Dialogue interview series. In this 90 minute interview with producer Mike DeLuca, Vardalos talks about how her experiences in the Second City comedy troupe helped her as an actress and a screenwriter, and how the unofficial "tell-the-Greek" word-of-mouth pr