The Pittodrie outfit have not won in the SPL since the dizzy heights of beating champions Celtic 4-2 in January and Calderwood admits Hamilton pose another stern test for his players.
"Hamilton always give us a tough game," he said.
"We were poor when we played them at the start of the season and we gifted them two goals. We didn't really turn up when we played them in January at New Douglas Park either.
"They have beaten us twice this season and we certainly want to avoid a third defeat."
The Dons have drawn their past four games, despite creating enough chances to pick up victories on each occasion.
Calderwood believes the injured duo of Lee Miller and Gary McDonald, who will both miss Saturday's match, have been a massive loss to his attacking ammunition.
He said: "Lee and Gary are a huge source of our goals, which makes life very difficult for us when they are out. But when we go 1-0 ahead we shouldn't be drawing games with the quality of players that we have.
"We aren't losing many games but not picking up all three points is costing us big time at the moment."
The Dons have a difficult week ahead with a Homecoming Scottish Cup quarter-final replay with Dunfermline on Wednesday before a trip to Hibernian next Saturday.
Calderwood knows there is huge pressure on his side to win all three games in order to ensure their Scottish Cup and league ambitions remain on track.
But the Dons boss says that level of expectancy is just part and parcel of being at a club like Aberdeen.
"This will be the 200th week in a row that has been crucial for us!" he joked.
"We get used to that sort of pressure at Aberdeen - that is why we are here at the end of the day."
The Dons will start as favourites against a Hamilton side that could have up to eight players unavailable through injury and suspension.
But Calderwood said his players will still have to be wary of the under-strength Accies as such circumstances have a tendency of bringing a team closer together.
He added: "I remember last year we had nine players out when we played a very good Dundee United side and we still won.
"They will come up here with nothing to lose and, in a strange way, it sort of galvanises you when things like that happen.
"This is probably one of their last chances to get some points if they want to make the top six so we will be expecting a tough game."