A sequel to The Boondock Saints (1999), the film stars Sean Patrick Flanery, Norman Reedus, Clifton Collins Jr., Julie Benz, Peter Fonda, and Billy Connolly.

Set eight years after the events of the first film, it follows Irish fraternal twin brothers Connor and Murphy MacManus (Flanery and Reedus) living a quiet life in Ireland with their father Noah, formerly known as "Il Duce" (Connolly).

However, when an assassin frames the twins for the murder of a Catholic priest, they return to Boston and join forces with Mexican underground fighter Romeo (Collins, Jr.) and FBI Special Agent Eunice Bloom (Benz), a former protégée of Paul Smecker.

Father Sibeal arrives in Ireland to inform his nephews the MacManus twins, Connor and Murphy, that someone has copied the style of execution they used 8 years earlier to kill Mafia boss Joe Yakavetta.

En route to Boston aboard a container ship, the twins meet a Mexican underground fighter named Romeo, who recognizes them as the Saints.

Hearing a radio broadcast regarding Joe's son, Concezio Yakavetta, they deduce that he must have hired the hitman who killed the priest to draw them out of hiding.

They are intimidated by the appearance of charismatic FBI Special Agent Eunice Bloom, a no-nonsense protégée of the late Paul Smecker, who has been assigned to determine whether or not the Saints are responsible for the murder.

Expertly analyzing the crime scene, Bloom concludes that the Saints did not murder the priest, and begins an investigation to find the real assassin.

Fantasizing that they are action movie stars, Connor, Murphy, and Romeo hit a warehouse that is being used by a Chinese Triad gang to process heroin for Yakavetta.

Bloom interrupts Yakavetta's inept caporegime "Gorgeous George" while he's receiving a massage, smacking him on the rump with a paddle, displaying her credentials.

The site's consensus reads: "This sequel to the cult favorite The Boondock Saints is more of the same -- unoriginal, absurd, violent, over-the-top, and occasionally mean-spirited".

[citation needed] The soundtrack became available for preorder in late March on the official Boondock Saints Store website and became available for purchase and digital download at other retailers April 7, 2010.

[17] Again, on February 26, 2013, Troy Duffy stated that he was getting together with Norman Reedus and Sean Patrick Flanery to resume talks about Boondock Saints 3, in hopes that they could make the film a reality for fans.

[19] On May 6, 2017, Sean Patrick Flannery announced on Twitter that he and Norman Reedus had walked away from production of Boondock Saints III with no further explanation, leading the future of the series in doubt.

[20] In November 2021, a third Boondock Saints film was officially announced, with Reedus and Flanery reprising their roles as Connor and Murphy MacManus and Duffy returning to direct.

Reedus and Flanery will reprise their roles and serve as executive producers, although Duffy, who plans to continue the story through a series of books, will not return as director.