- Directors: Troy Duffy
- Producers: Chris Brinker, Don Carmody
- Writers: Troy Duffy
- Genres: Action, Crime, Drama, Thriller
- Actors: Sean Patrick Flanery, Norman Reedus, Clifton Collins Jr, Julie Benz, Judd Nelson, David Della Rocco, Peter Fonda, Billy Connolly
It is revealed that after the MacManus brothers, Connor (Sean Patrick Flanery) and Murphy (Norman Reedus), and their father Noah (Billy Connolly) assassinated Papa Joe Yakavetta, they fled to Ireland and remained in a secluded farmhouse for the past eight years. Their uncle Sibeal arrives to inform them that a renowned Boston priest they heard of was murdered by a mysterious assassin who attempted to copycat their method. In response, the brothers dig up their old clothes and guns and prepare to depart back to Boston. On a freighter en route to Boston, they meet a Mexican fighter named Romeo (Clifton Collins, Jr.) who admires the saints and offers his resources in Boston if he is allowed to join them, and they accept. They hear a radio broadcast regarding Papa Joe’s son Concezio Yakavetta (Judd Nelson) and deduce that he is the man who hired the hitman to kill the priest and draw them out of hiding.
Meanwhile, Detectives Dolly (David Ferry), Duffy (Brian Mahoney), and Greenly (Bob Marley) are at the scene of the priest’s murder and become worried that their involvement in the murder of Papa Joe will be revealed. They are greeted by Special Agent Eunice Bloom (Julie Benz), the protege of Paul Smecker (Willem Dafoe), and investigate the death of the priest. All four are correct in their assertion that it was not the Saints who murdered him, as the gun angles, exit wounds, and placement of pennies don’t match their M.O., plus the fact that they don’t kill the innocent. They begin an investigation to find a man of short stature who fits the description of the assassin and find that all signs point to Concezio Yakavetta, who is still angry over the circumstances of his father’s murder. However, the assassin appears to be working for a mysterious old man, not Yakavetta, who apparently knows Noah and is trying to bring him out of hiding by having the brothers killed.
At an unknown location, Bloom meets with Sibeal regarding a place to hide. The boatman waiting to take her there is revealed to be Paul Smecker, who faked his death and secretly set up a chain of resources to assist the Saints. They plot to break the Saints out of Hoag Maximum Security Prison and have them do what they do on a larger scale. In the meantime, Connor and Murphy plot to kill as many fellow prisoners as they can while they wait to be freed.