- Fake American: Chris Hemsworth, who is from Australia, adopted a U.S. southern accent to portray his character.
- The Other Darrin:
- With this film, Ed Helms becomes the fifth actor to play Rusty Griswold, after Anthony Michael Hall, Jason Lively, Ethan Embry, and Johnny Galecki.
- Leslie Mann also takes over the role of Audrey from Dana Barron.
- In the Canadian French dub of Vegas Vacation, Rusty, Audrey, and Ellen were voiced by Joël Legendre, Aline Pinsonneault, and Marie-Andrée Corneille respectively. Here, they are instead voiced by Frédéric Paquet, Viviane Pacal, and Élise Bertrand, again respectively.
- Role Reprise:
- Chevy Chase and Beverly D'Angelo return as Clark and Ellen Griswold.
- In the Canadian French dub, Clark is voiced by Jacques Lavallée, reprising his role from Vegas Vacation (which is the only other movie in the series besides the 2015 one to have a Canadian French dub).
- Sequel Gap: The film came out 18 years after the previous film, Vegas Vacation; and 32 years after the first Vacation.
- What Could Have Been:
- Anthony Michael Hall, Ethan Embry, and Johnny Galecki were offered to reprise their role as Rusty Griswold for this film, but declined. Afterwards, Will Ferrell, Michael Rosenbaum, Adam Sandler and Jason Sudeikis were considered for Rusty before Ed Helms was eventually cast.
- Dana Barron was also asked to return as Audrey before Leslie Mann took the role.
- A previous synopsis of the movie had Walley World closing permanently.
- Randy Quaid couldn't reprise his role as Cousin Eddie, due to his arrest involving a house payment dispute. Quaid currently lives in Canada. His character does get a mention.
- You Sound Familiar: In the Canadian French dub, Debbie is voiced by Aline Pinsonneault, who previously voiced Audrey in Vegas Vacation.
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