On February 7, 2012, Cignetti was hired by the St. Louis Rams to be their quarterbacks coach. Cignetti worked with Sam Bradford, the third-year signal caller who set new career highs in passing yards (3,702), touchdown passes (21) and Passer rating (82.5) in 2012. On February 12, 2015, Cignetti was promoted to offensive coordinator, he held that position for 12 games. On December 7, 2015, Cignetti was fired by the Rams, the Rams rank 31st in yards per game (296.3), 32nd in passing yards per game (178) and first downs (175), and tied for 30th in offensive touchdowns (18).