The 2006 Major League Baseball All-Star Game was the 77th playing of the midseason exhibition baseball game between the all-stars of the American League (AL) and National League (NL), the two leagues comprising Major League Baseball. The game was held on July 11, 2006 at PNC Park in Pittsburgh, Pennsylvania, the home of the Pittsburgh Pirates of the National League. The contest was the fifth hosted by the city of Pittsburgh – tying the Cleveland Indians for the record of most times hosted by a single franchise. The game resulted in the American League defeating the National League 3–2, thus awarding the AL champion (which was eventually the Detroit Tigers) home-field advantage in the 2006 World Series.

As with each All-Star Game since 1970, the 8 starting position players (with no designated hitter due to playing in an NL stadium) of each league were elected by fan balloting. The remaining players were selected by a players' vote, each league's team manager, and the All-Star Final Vote to add one more player to each roster. In all, 32 players were selected to each league's team, not including players who decline to play due to injuries or personal reasons.

The game was the fourth straight All-Star Game to decide home-field advantage in the World Series. The AL entered the game on a nine-game unbeaten streak (eight wins, with one tie in 2002). Many analysts saw the disparity between the leagues as more pronounced than ever this season, particularly due to the AL's dominance during interleague play, compiling a 154–98 record, the best record for either league in the ten-year history of interleague play.

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