The UAE Team Emirates leader had lost time on almost every mountain stage and found himself down in 27th place overall at the start of Friday's stage, more than 45 minutes down on race leader Simon Yates. Chris Froome (Team Sky) went on to win stage 19 and move into the overall lead.
The team confirmed the exit on Friday, with no indication that Aru was suffering with illness or any other problem. The team later released a comment from Aru.
"I’ll evaluate my feelings day by day because I feel that I'm going through an abnormal period of my sporting career. I wanted to keep going and honor the team's jersey, give the fans something and the race its due respect. But I could not do it. I'm really sorry for all this, for my team, my family and the sponsors that I represent, but it didn't make sense to go ahead," Aru said.
"I’m not going to be dramatic, this is sport and maybe, even if it hurts to say so now, this is the beauty of the sport. I'll try to reset and understand together with the team what happened, then I'll restart thinking of the rest of the season. Because this is what you have to do in difficult moments."
There were high hopes of Aru, the Italian champion, heading into the 2018 Giro. After two disappointing attempts at the Tour de France, it was thought a return to his 'home' Grand Tour could inspire him to rediscover his 2015 form, when he finished runner-up at the Giro and then won the Vuelta a España.
Yet his struggles were evident from early on. He lost a chunk of time, quite expectedly, on the opening-day time trial in Jerusalem, and although he finished with the favourites on Mount Etna on stage 6, he lost more than a minute on the stage 9 summit finish at Gran Sasso.
The second weekend saw any faint hopes of a podium evaporate. While losing two minutes on Monte Zoncolan on stage 14 was far from ideal, it was nothing compared to the 19 minutes he shipped on the following day's stage to Sappada. That left him 22nd overall, 25 minutes down.
After the final rest day, a remarkable resurgence seemed on the cards when Aru finished sixth on the 34.2km stage 16 time trial, though it soon emerged how he might have achieved such a surprising result against the clock as he was penalised for drafting.
Aru finished 112th on stage 17 and 122nd on the summit finish at Prato Nevoso on stage 18, and it was unclear if the legs were empty or if he was saving himself for an assault on stage wins in the final two big mountain stages, carrying on the form that had been hinted in the time trial.
The question was answered just over an hour into Friday's big mountain stage, before the riders had hit the highly anticipated Colle delle Finestre and onto Sestriere, scene of a famous stage win for Aru at the 2015 Giro.