Often compared to former teammate Johan Santana, another hard-throwing lefty, Liriano was touted as one of the "super-prospects" within the Twins organization. As a member of the Rochester Red Wings, Minnesota's Triple-A farm club, Liriano was awarded the 2005 International League Rookie of the Year. He led all minor league pitchers in strikeouts that year, with 204. He made his major league debut in relief on September 5, 2005, against the Texas Rangers. He later joined the Twins' starting rotation and won his first game on September 30, 2005, against the Detroit Tigers. Liriano started the 2006 season in Minnesota's bullpen, but was promoted to the starting rotation in May, exchanging positions with struggling starter Carlos Silva. He won each of his first three starts.