Dean Richards says Newcastle are "absolutely raring to go" as they target their first appearance in a European final.
The Falcons head to Aviva Premiership rivals Gloucester on Friday, having already won at Kingsholm this season in the league.
The winners will face Cardiff Blues or Pau in next month's Challenge Cup final, and Newcastle rugby director Richards does not want to see his team suffer semi-final agony for a second time this season.
Newcastle lost an Anglo-Welsh Cup semi-final to Exeter in March, and Richards said: "It really annoyed me because I love winning, and we were within reach of a final.
"We didn't turn up on the day, we probably didn't pay Exeter enough respect, and that certainly won't be the case on Friday.
"It is all about understanding who we've got, what they can do and then going out and delivering what we have talked about.
"There are a few changes due to injuries, guys coming back and some boys not being registered for Europe, but the upshot is that we have fresh legs taking the field and a group of guys who are absolutely raring to go."
Scrum-half Michael Young will captain Newcastle instead of an injured Will Welch, with Maxime Mermoz and Josh Matavesi forming the centre partnership, lock Sean Robinson replacing Will Witty and back-row pair Evan Olmstead and Ryan Burrows also gaining starts.
Gloucester will bid to reach a third Challenge Cup final in four seasons, having won the trophy three years ago and then losing to Stade Francais last term.
Head coach Johan Ackermann has made a number of changes from the side that beat Premiership opponents Harlequins last weekend.
Wing Tom Marshall returns to action, replacing Charlie Sharples, while it is all change in the front-row with Paddy McAllister, Motu Matu'u and Fraser Balmain starting, and lock Mariano Galarza and flanker Ruan Ackermann also feature.
"There is obviously a lot at stake, and both sides showed some good qualities last weekend," Johan Ackermann said.
"We've played each other three times already (this season), so it is not an unknown factor. Both teams know each other quite well, so it makes the contest quite intriguing.
"Newcastle are the one side to come and beat us at Kingsholm in the league, which shows their quality, but we went there and beat them. So, it just shows how well-balanced the two teams are.
"We can't afford any complacency. The reality is that they will come down with a lot of confidence, as they are doing well in the Premiership and have beaten us here before.
"We have to make sure that we get out of the blocks."