He made his Major League debut on April 4, 2005 against the Detroit Tigers, allowing two runs in 2 innings.

Under the terms of Rule 5, Sisco remained on the Royals major league roster for the entire 2005 season so that he would not have to be offered back to the Cubs for $50,000.

Sisco signed a minor league contract with an invitation to 2011 spring training with the New York Yankees.

[2][3] He finished the season with the Piratas de Campeche in the Mexican Baseball League, where he was 1–2 with an 8.27 ERA with 10 appearances.

In 2013, Sisco played the first half-season for the EDA Rhinos, a team in Taiwan's Chinese Professional Baseball League, where he is primarily used as a starting pitcher.

[5] Sisco re-signed with the EDA Rhinos of the Chinese Professional Baseball League following his release from Korea.