The episode introduces a new regular cast member to the series, Odette Annable, who plays Dr. Jessica Adams.
[5] Jaleel White, who played Steve Urkel on the ABC show Family Matters, makes a guest appearance in the episode.
[7] Eight months after being imprisoned for driving his car into Cuddy's living room, House has five days before he is granted parole, to which he has become eligible due to space issues and relatively good behavior.
[11] Anthony Ocasio of ScreenRant.com gave the episode a positive review, stating "the House season 8 premiere presents a wonderfully crafted case study, penned by executive producer Peter Blake, on the man that is House, in which Hugh Laurie masterfully traverses a new environment filled with intriguing challenges and compelling characters.
Oliveto commented that Twenty Vicodin was "A tense season-opener [that] assures us that “House” hasn’t lost the magic".