Mitrione was born in Bloomington, Illinois and raised in Springfield, where he attended Sacred Heart-Griffin High School for first four years, where he competed in football, swimming and diving, and track and field. He graduated from Springfield Southeast High School. In football, he received Honorable Mention USA Today All-American & All-State honors in his senior year playing defensive line. He also trained in Shotokan Karate as a child to help deal with his extreme hyperactivity.
Mitrione competed in Toughman Contests while he was still in high school, and finished second in his initial Toughman Contest in his hometown of Springfield. He attended Purdue University on a football scholarship and started 35 consecutive games for the Boilermakers at defensive tackle, but broke his right foot during winter conditioning practice in his senior year. Mitrione went undrafted during the 2002 NFL Draft, but was offered a contract by the New York Giants.
After again injuring his foot in a 2003 playoff loss to the San Francisco 49ers, Mitrione had seven surgeries to his foot including one that extended his Achilles tendon, and was in crutches for 16 months. Mitrione was released by the Giants in 2004 and then had brief stints with the San Francisco 49ers and Minnesota Vikings, before being released by the Vikings six weeks into the 2005 season and a week before his first child was born.[citation needed]

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