The Heineken Cup quarter-final between Saracens and Ulster will take place at Twickenham on April 6.
Saracens chairman Nigel Wray has admitted his delight at playing "at the home of English rugby", with the winner set to face either Toulon or Leicester Tigers in the semi-finals.
"We look forward to playing this important match at the home of English rugby, a ground that many of our players know extremely well," Wray told the club's official website.
"It is absolutely clear that people want to see big teams playing big matches at big stadiums, and that is precisely what we will deliver at Twickenham.
"We did consider the option of playing this showpiece match at Allianz Park, our brand new home stadium in NW4, but, in consultation with local residents and our partners at the London Borough of Barnet, we have decided to settle at the new venue before applying to stage a one-off event with a larger capacity."
According to Saracens' official website, tickets will be made available for general sale on February 18.
