Both sides are locked on 14 points apiece in the league and they are equally as close off the field given that a number of players have turned out for both Irish provinces.
Schmidt though expects his team to be less hospitable than they were in their 26-7 win over Aironi on Saturday after a sluggish start allowed the Italians to lead at the break.
Schmidt said: "It's a huge local derby with them being just down the road in Galway.
"A lot of our players have played there and a lot of their players have played a bit here and the players know each other pretty well. They're like brothers. They're best of buddies except on the field.
"We certainly need to start better than we did on Saturday. We can't afford to give Connacht so much latitude and not expect to get a loss on the board.
"I think we were a little bit unlucky that Isa (Nacewa) had an off day with the boot but you've just got to go back and get another few tries and thankfully that's what we did in the second half.
"They'll come here with confidence, they got a bonus point at Ospreys which is a lot better than we did, and they've really been very difficult to beat so far this season
"It's winner takes all, winner stays in the top four and the other one will probably drop out."
Schmidt will welcome back four key men from the treatment table for the clash at the RDS as his side look to make it three wins in a row.
Kevin McLaughlin and Dominic Ryan both return from ankle injuries, Nathan White is back after a calf strain and Ben Marshall has now recovered from knee damage.
Schmidt added: "All four are training with us which is a real positive, those guys give us some strength in depth because we were getting a little short, particularly in the back row."
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