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Tyrell is encountered in the Raccoon Hospital in the main game, during when the player is controlling Carlos Oliveira. He can be encountered in two different scenarios, however, depending on what floor the player chooses to head to first. Should the player go to Basement Level 3, Carlos will first be held up by a wounded Tyrell, who suspects that Carlos is going to kill him. Tyrell admits to being one of the Supervisors; a secret part of the U.B.C.S who were to observe the effects of the B.O.W's against the soldiers. Tyrell also lets loose Nicholai Ginovaef's true intentions as a Supervisor as well, and how he is going around killing the remaining Supervisors to increase his pay.
Meanwhile during the exposition, Tyrell is attempting to unlock a safe, but upon doing so finds a bomb inside that kills him, with Carlos himself only just managing to escape the blast.
Should the player head to the fourth floor first, Carlos will find Tyrell now at the mercy of Nicholai. Nicholai explains his intentions and readies his weapon at Carlos, but not before Tyrell pulls out a grenade planning to kill them. Carlos manages to escape the blast, while Nicholai dives through a window--to which he also somehow survives, as proven by his appearances later on even with this event set in place.