His common nickname is "Everyday Eddie", a testament to his durable arm during his first stint with the Twins. Over Eddie's career, he appeared in 908 games. Only 22 other pitchers have appeared in more games.
Guardado was drafted by the Minnesota Twins in the 21st round (570th overall) of the 1990 Major League Baseball draft. For several years, the Twins attempted to use Guardado as a starter, but in 1996, he was converted exclusively to a relief pitcher and did not start another Major League game. That season, he led the majors in games pitched with 83. In September 2001, Guardado became the Twins' closer, replacing LaTroy Hawkins. In 2002, he broke Rick Aguilera's 11-year-old Twins team record for games saved, saving 45 games. He followed that up with 41 saves in 2003. After that season, he became a free agent.
On December 9, 2003, Guardado signed a one-year contract with the Seattle Mariners worth a guaranteed $13 million. The deal also included player and team options for the 2005 and 2006 seasons. In 2004, Guardado saved 18 games and posted a 2.78 earned run average in 41 appearances, but suffered a torn rotator cuff and missed the last two months of the season. In 2005, he set the Mariners' record for consecutive saves at 27, which was later broken by J. J. Putz. On May 4, 2006, after three blown saves in less than three weeks, Guardado was temporarily removed from the closer role with the Mariners. Manager Mike Hargrove stated, "We're just trying to get him to step back from the edge a little bit, get himself going a little bit so we can get him back out there again and be the closer like we know he can."

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