In addition to Spiezio's pivotal moment helping the Angels win the World Series, 2002 was also his most productive full season, with a .807 OPS.

Playing every day, he set career highs in batting average, on-base percentage and RBI.

On February 18, 2006, Spiezio signed a minor league contract with the St. Louis Cardinals with an invitation to the club's spring training.

Spiezio played well enough during the Cardinals' exhibition to secure a roster spot with the team as a reserve infielder entering the 2006 season.

With the Cardinals trailing, 6–4, in the seventh inning of Game 2 of the 2006 National League Championship Series, Spiezio hit a two-run triple to tie the score.

On November 16, 2006, Spiezio signed a two-year contract to return to the Cardinals until the end of the 2008 season, with a club option for 2009.

[4] On June 15, 2007, Spiezio took the mound as a relief pitcher in the bottom of the eighth inning of a lopsided loss against the Athletics.

After having pitched in one game, Spiezio played six positions in his career (seven counting designated hitter), missing catcher, shortstop, and center field.

[7] On September 14, 2007, Spiezio was removed from the restricted list after 36 days and also reactivated to play in that evening's home game.

In April, he pleaded guilty to two misdemeanors and was sentenced to three years' probation and 80 hours community service.

[11] Spiezio later said that while he was sober at the time, he was in a deep depression after being released by the Cardinals and wasn't ready to take the field.

The Angels put him in touch with the Orange County Flyers of the independent Golden Baseball League.

Flyers manager Phil Nevin, a former major leaguer, decided to sign Spiezio after letting him work out for a week and getting assurances he was mentally ready to play.

On April 7, 2015, at 2:30 AM, police in Ottawa, Illinois, responded to a call that Spiezio punched out a window at the apartment where his then-girlfriend and infant son lived.

Spiezio fled police and was later found through the use of a K-9 tracker behind a building, resulting in him being tased in order to be brought into custody.