The Cardinals named Lilliquist as the Cardinals major league bullpen coach on November 2, 2010. Late in the Cardinals' 2011 World Series–championship season, he temporarily replaced incumbent pitching coach Dave Duncan, who took a leave of absence for family reasons. On January 6, 2012, the Cardinals announced that Lilliquist would permanently replace Duncan, whose future remained uncertain. On October 3, 2017, the Cardinals announced that Lilliquist would not return to the team for the 2018 season.