Cardiff Blues have moved their Heineken Cup match with Leicester Tigers on 29 October to the Millennium Stadium.
The Millennium Stadium in Cardiff can hold 75,000 spectators
The Blues experimented with using the 75,000-capacity national stadium in a match with Leinster last season.
That was prompted by the Blues' Arms Park home being covered by a marquee used for FA Cup final hospitality.
They were rewarded with a Celtic League regular season record crowd of 15,327, with a match against English giants the Tigers promising to be much higher.
Leicester are double Heineken Cup champions and will welcome the chance to play at the same Millennium Stadium where they last lifted the trophy, beating Munster 15-9 in the 2002 final.
Robert Norster, the Cardiff Blues chief executive, said: "The event will provide the opportunity for many more to watch the Cardiff Blues take on one of the powerhouses of European rugby in one of the world's finest stadiums.
"We have taken the decision as last season's match at the national stadium was recognised to be a great success by the overwhelming majority of our traditional and newer supporters."