The 2017 champion was passed fit to race by Team Sunweb after sustaining nasty injuries on Tuesday, but the Dutchman took the decision to abandon on the soggy roads in Frascati.
Dumoulin finished over four minutes adrift on Stage 4 after he was wiped out in a ripple-effect crash six kilometres from the end. He eventually crossed the line as blood streamed down his left leg, surrounded by his Team Sunweb teammates.
Dumoulin's 2021 season over after breaking wrist on training ride
He will now focus on preparing for the Tour de France.
Speaking on Eurosport’s new analysis show The Breakaway on Tuesday, Dumoulin’s teammate Nico Roche debated what the options will be now for the team leader:
Do we give up and refocus on the Tour or do we stay and hope things go better for two options: do we try and save the Giro by going for the stage, or is it not too bad and I can still fight and maybe in the second or third week go for a top ten?
Dumoulin was 4:30 behind maglia rosa incumbent Primoz Roglic.
'It was okay until I stood up on the pedals' - Dumoulin talks about withdrawal
‘Absolute masterclass’ – Bahrain Victorious delight as Mohoric wins final stage, Colbrelli tops GC
Dumoulin to take part in World Championships