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The home side looked dangerous from set pieces but it was the Premier League side who threatened from open play, although an Antonio Valencia cross for Adnan Januzaj ended up in the hands of Chris Dunn.
The League Two side had a good chance to open the scoring before the break when Michael Nelson attempted to head in from a corner, but his finished was blocked by teammate Josh Coulson, who could then only head over.
Januzaj tried to get the visitors off to a quick start in the second half as he attempted to squeeze the ball in from a tight angle after a header on from Phil Jones, but the keeper held firm.
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Van Gaal sent Robin van Persie on for the final 20 minutes in a bid to force a winner, but the Dutch international spurned his first chance, slicing his shot well high.
Ander Herrera also came on late to try to avoid the replay for the Premier League side, but he was unable to find Falcao and Van Persie in the box after making a run down the right flank.
Having defended for much of the second half, Cambridge went on the attack in the final five minutes, but David de Gea kept Donaldson's strike out.
Dunn had to make a double save in stoppage time as the visitors piled forward late on, but Januzaj and Van Persie were both denied before Cambridge scrambled the ball clear.
The result ensures that both sides will go into the draw for the fifth round of the Cup on Monday, and they will meet again at Old Trafford.