Troy Duffy wrote the part of Romeo, the Saints' sidekick, specifically for his friend Clifton Collins Jr.. Coincidentally, the part of Rocco, the sidekick in the first film, was written specifically (and named for) actor David Della Rocco.
When the brothers meet Rocco at the bar in their dream, a black cat walks past Rocco across the counter. The cat is a sly reference to Rocco's girlfriend's cat Skippy, who Rocco accidentally shot in the first film.
In Noah's voice-over during the drug factory flashback, he says "While the wicked stand confounded, call me, with thy saints surrounded." In the first movie, that line is painted above the Irish flag on the wall in the arms dealer's warehouse.
Three actors in this film have both starred in movies from the Saw film series. Julie Benz and Joris Jarsky in Saw V and Sean Patrick Flanery in Saw 3D. Another actor from the first Boondock Saints was also in Saw V, Carlo Rota.