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Normal - The default mode of the game. Enemies have more health. Bosses are tough and attack frequently. The player also takes more damage.
Lesser demons and bosses health: 100%
Lesser demons and bosses damage: 100%
Hard - Unlocked by beating Normal. Enemies have even more health and deal more damage. Bosses attack more frequently.
Lesser demons and bosses health: 175%
Lesser demons and bosses damage: 175%
Very Hard - This difficulty is only available in the Special Edition version of the game. It is unlocked by beating the game on Hard. Bosses attack even more frequently. The player deals less damage and takes more damage from enemies. It introduces the enemy waves and boss patterns used in Dante Must Die mode.
Lesser demons and bosses health: 200%
Lesser demons and bosses damage: 200%
Dante Must Die/Vergil Must Die - This difficulty is unlocked by beating the game on Hard. Enemies are hostile and deal more damage. They also have access to Devil Trigger and activates it after a certain period of time. Vergil Must Die is only available in the Special Edition version of the game.
Lesser demons and bosses health: 250%
Lesser demons and bosses damage: 250%