In this remake, there are two new enemies that weren't in the original or director's cut: Crimson Heads zombies and Lisa Trevor. Creature designer Masaki Yamanaka felt that traditional zombies were getting old, so their revival as stronger and faster Crimson Head zombies (as well as ways to prevent their resurrection) added fresh kinds of terror and gameplay elements. Lisa came about because director Shinji Mikami suggested to introduce a new type of boss enemy with a unique look and sound. The decision to connect this monster to the new Trevor subplot in the game informed much of Lisa's character and backstory.
A full remake of the original Resident Evil (1996), the new version includes an altered mansion layout with brand new rooms and enemies and new plot elements that take into account developments in the later Resident Evil/Biohazard games. Also, the entire script was retranslated, a new voice cast hired and all cutscenes rendered as computer-generated FMVs (rather than live-action); this eliminated the notoriously poor acting and English dialogue that was present in the original, from a combination of translation issues, non-professional actors and improper voice direction. Nevertheless, script translator Shinsaku Ohara, a native English speaker, was hesitant to make any changes, as he was a fan of the more campy original dialogue.
In the original Resident Evil (1996), animations of opening doors or ascending/descending stairs were added between areas to mask the time needed for the console to load the data for the next room. Even so, each room could only consist of up to eight backgrounds, so loading screens were sometimes necessary to move between upper and lower levels in the same room. Since the GameCube was powerful enough to not need any loading screens, this remake originally didn't have them. However, fans disliked this decision, so Capcom put them back in to maintain the suspense, except for most of the stair animations.
The devices in which you have to put the MO discs in (to release the door to the prison cell) are actually slightly modified GameCube consoles.
The boss battle with the giant mutated snake and the first encounter with the Tyrant are largely unchanged from the original. The boss battle with the giant shark has been changed from a typical battle to a puzzle. In the final battle, to prevent players from simply running in circles and shooting the Tyrant from afar (like they did in the original), the Tyrant was programmed to attack the NPCs, forcing the player to intervene and save them at the risk of their own lives.