Harlequins director Conor O'Shea admits that the Double Header and contests with London Irish are 'never comfortable.'
The former Ireland full-back has a rich history with the Exiles, having playing and coached the club in the past before beginning a successful era with Harlequins.
The 2012 champions will kick off the new season over the road at Twickenham but haven't had it easy in the first game of the campaign in recent times, sneaking past Wasps by two points and one point respectively in the last two years, including a thrilling 42-40 win in 2012.
"The Double Header is never comfortable and it's never comfortable against London Irish," said O'Shea.
"The last two have been horrific - we've won both of them but they've been horrific.
"Smithy [Irish director of rugby Brian Smith] is doing a great job up there and they've got a new training centre. Tom Guest has gone there and we wish him luck.
"It will be a tough game, it always is, they've recruited very well and every team in this Premiership can beat anybody.
"Be prepared for the usual trials and tribulations.
"We'll strive to be the best we can be and if we are, we've got good players who will take us to where we want to be.
"Our games with London Irish are always tight and decided by little things. We lost to them in the opening five games last year down at the Madejski Stadium and that was a blow.
"They've got good players and you can look through their team and they've got an international tight five. We'll have to be on our game and hit the ground running."