She not only struck out at her foes physically, but battered them emotionally as well, stirring within each of them memories of loss, sadness, betrayal, regret, guilt, even as she fed upon on their anger and relished in their despair. The brief, yet horrific Reign of Anguish-reign did not last long however, as a group of heroes pursuing Diablo stormed the monastery, eventually coming to face off against Andariel on the fourth level of the catacombs.

She sent the Slayer to guard the path between Waystruck and the Rogue Citadel. By the time Diablo arrived and passed through the Eastgate Keep, Andariel's position of power was well solidified. Her foul magics corrupted part of the nearby Dark Wood. During the assault on the Rogue Monastery, many sisters were slain and others were turned to serve Andariel herself. Andariel was thus sent by Diablo himself to invade the citadel of the Sisterhood of the Sightless Eye in order to close the passage through the mountains into the desolate eastern lands of Aranoch. Therefore, they endeavored to gain favor with the Lord of Terror by protecting his human host. Andariel and Duriel concluded that the Primes would inevitably reclaim their position in Hell. Nearly three hundred years after the Dark Exile, Diablo finally escaped from his captivity beneath the Tristram Cathedral, heading east to reunite with his brothers, Mephisto and Baal.

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