Agnew debuted with the St. Louis Browns on April 10, 1913. In 105 games his rookie season, Sam hit .208 with 2 home runs and 24 RBI, stealing 11 bases, in 307 at bats. In 1914, Agnew hit .212 with 16 RBI in 115 games. That season he finished 23rd in the balloting for Most Valuable Player, losing out to Eddie Collins of the Philadelphia Athletics. In 1915, he slipped down to a .203 average with 19 RBI in 104 games.\n', '

On December 16, 1915, the Boston Red Sox purchased Agnew from the St. Louis Browns. Serving as the backup to regular backstop Pinch Thomas, Agnew hit .209 (14-for-67) with 7 RBI in 40 games. Splitting time behind the plate with Thomas in 1917, Agnew hit .208 with 16 RBI in 85 games. Although he was considered the regular catcher in 1918, Agnew struggled at the plate, hitting just .166 with a career-low 6 RBI in 72 games. His offensive woes continued during the 1918 World Series, as he went hitless in nine at bats over four games against the Chicago Cubs.\n', '

In January 1919, Agnew was purchased from the Boston Red Sox by the Washington Senators. In just 42 games, Agnew hit a career-high .235 with 10 RBI. He played his final major league game on September 28, 1919. After his playing career, he went on to become a pitching coach for the Cubs and also a minor league coach.\n', '

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