This movie takes place between the events of Resident Evil 4 the video game and Resident Evil 5 the video game.

This is the first Resident Evil movie to be made in computer animation and is also canon with the video game series.

At the very end of the movie, before the credits roll, the company Tricell is briefly introduced, looking for any remains of the G-Virus. Tricell is more known in the next Resident Evil game, Resident Evil 5 (2009).

Claire Redfield, Leon Kennedy, and Ingrid Hunnigan are the only characters that come from the video game series, and voiced by the same actors.

The umbrella colors and patterns Claire brings with her to use as a possible weapon while looking for survivors in the airport resemble the logo of the Umbrella Corporation.  Claire even makes a comment about that.

The scene in which Claire and Leon meet, is a reenactment of how they met in Resident Evil 2 (1998). In that game: Leon runs towards the diner and sees Claire being faced off with a zombie. He say's "Get down!" and shoots the zombie. Claire then looks at his face as he offers her his hand. In the movie, Claire goes off to look for a survivor that she hears running around, she looks out the corner of a wall to hear Leon say, "Get down!" He shoots the zombies and offers Claire his hand as she says, "Leon!"

When Fredric Downing left his office with Claire inside, the sound effect of the door closing is exact same one used for doors closing in the earlier Resident Evil games.

Among all the Resident Evil games and movies starring Leon, this is the first, but not the last, one not to have Ada Wong as a secondary character.

Because Curtis Miller injected himself with the G-Virus, his mutated state greatly resembles the mutated state when William Birkin from Resident Evil 2 was infected.

Soundtrack clips from the Resident Evil 2 (1998) game are used in the theatrical trailer.

WilPharma is the corporation responsible for the biohazard in this movie. WilPharma stole the G-Virus sample and research from Umbrella after Raccoon City's ultimate destruction.

By the time this movie was released on physical media, the Blu-Ray disc contains trailers for Resident Evil 5 (2009) as bonus features.

After the time bomb goes off, Claire Redfield goes up the elevator to the control room. We can see a monitor on the right of the screen which resembles the single open eye motif used at the start of the first Resident Evil game.

This is the first Resident Evil movie to be created by its game developers, Capcom, instead of Sony and Screen Gems, which were the live-action movies.

Roger Craig Smith voiced the character of Curtis Miller. He would later go on to voice the character of Chris Redfield in Resident Evil 5 (2009) and Resident Evil 6 (2012). Also, Troy Baker, who voiced various characters in this film, would go on to voice the character of Jake Muller in Resident Evil 6.

Even with Umbrella and Raccoon City long gone, they're still referenced highly this movie.

Mistakes

When the central garden at WilPharma is incinerated, Leon and Angela escape through a drainage system and are fully submerged in water. A few seconds later, their hair and clothing seem perfectly dry.

During the Airport escape scene, one character armed with an M4 Carbine shoots continuously beyond the ammo capacity of his gun without ever reloading.

After the self-destruct system blows up, Claire suffers from an injury that causes her to limp a lot. Later on, after Leon defeats Curtis, Claire is no longer limping and appears perfectly healthy.