There had been speculation throughout 2007 that Boccieri would challenge U.S. Representative Ralph Regula to represent the 16th District in the U.S. House, a seat Regula had held for 36 years. When Regula announced his retirement in late 2007, Boccieri faced an open field. He defeated State Representative Mary Cirelli with 64% of the vote in the Democratic primary. He faced and defeated State Senator Kirk Schuring in the general election. He was the first Democrat to represent this district in 58 years.