This is the first Resident Evil game-canon title to take place in real world cities, like Chicago and New York City.

In the first scene you see a mansion identical to the Spencer Mansion in the first game, including the main hall and stairway.

This is the third Resident Evil CGI film to feature Leon S. Kennedy as a main protagonist, while this is Chris Redfield's first.

The sound effects of the lab doors in the university is the same sound effects of the lab doors in the Umbrella Chemical Lab in Resident Evil 2 (1998).

In some scenes, Rebecca is wearing the same S.T.A.R.S. medic uniform she wore in Resident Evils 0, and Resident Evil Director's Cut and Remake.

The first zombie Rebecca sees in her university is eating a dead victim's body, then looks back over his shoulder at Rebecca. This happened with the first zombie in both the original and remake Resident Evil game where it ate a victim, then looked back over its shoulder back either Chris or Jill then got up to attack.

Umbrella, Tricell, Raccoon City and the Los Illuminatos cult are mentioned a few times.

Features the first animated story appearance of Rebecca Chambers, her last in-game appearance before this film was Resident Evil Zero (2002). First released 15 years earlier.

When in the laboratory attack scene, Rebecca hides under a desk, she grabs a water bottle from it, to drink from whilst a zombie attack is underway, scriptwriter Fakami was insistent it not be cut, as in the whole film "there's a lot of different fetishes involved .. she looked so sexy drinking it; she pops her head out after drinking; she looks so cute, like a hamster."

Arias salvaged the resources of both Albert Wesker's Tricell and Carla Radames' Neo-Umrbella organizations. Showing that The Family did not do too well purging Carla's legacy; nor was Tricell properly dealt with after Wesker and Excella died.

Chris asks Leon if he's just going to sit around doing nothing for another week while Leon is drinking heavily, and Leon answers "I never plan that far ahead." This is a reference to Rick Blaine's answer in Casablanca.

The motorcycle Leon is riding has license plate NORTH AMERICA/BSAA-752.

So far, Leon has appeared in every Resident Evil CGI movie.  He even appears in the next CGI movie Death Island.

The first Resident Evil CGI movie not to feature singer Anna Tsuchiya during the end credits.

This is by far the most brilliant virus in the Resident Evil universe. As it can be placed dormant in people, activated and cured. Plus though who vaccinate themselves with the cure are recognized as allies to the infected.

Chris and Arias have their fight laughed at in online comments, who state the fight is what happened when the worst shots are the only ones left. The two miss point blank range shots nonstop.

In the commentary for Vendetta, Fukami Makoto, the writer mentions that he had written Nadia's background and that she is a lesbian, with a partner in San Francisco.

Mistakes

The grandfather clock in the mansion chimed once at 3:00.

In all firefights, there is seemingly unlimited ammunition in the respective magazines. Both in rifles and especially in handguns.

Misspelled credit: Dialouge Editer (should be Dialogue Editor).