In total 17 riders have so far withdrawn after a brutal first week at the world's greatest race. FDJ-Big Mat team boss Marc Madiot telling Reuters: "It has not been cycling, it has been Rollerball."
Canadian Hesjedal had talked up his chances in the three-week event but a leg injury on Friday's sixth stage has ended the Garmin rider's participation as he now looks to get fit for the London Olympics at the end of the month.
"It's very disappointing to leave the Tour this way. I was in good form and feeling comfortable, just really settling into the first week with an eye on the mountains," the 31-year-old, who lost over 13 seconds in the crash, said in a Garmin statement.
"I'll go home, keep working with the medical staff on my recovery, and refocus everything on the Olympics."
Triple-world champion Oscar Freire and Wouter Poels broke ribs and suffered internal injuries in Friday's crashes but remarkably finished the stage before withdrawing.
Garmin's Tom Danielson is also in hospital following the pile-up and is out of the race along with Davide Vigano, Mikel Astarloza, Imanol Ervitti, Jose Ivan Gutierrez, Hubert Dupont, Amets Txurruka and Maarten Wynants. Frenchman Anthony Delaplace decided to start Saturday's seventh stage to the peak at La Planche des Belles Filles with a broken bone in his wrist and his arm but soon had to give up.
Garmin team boss Jonathan Vaughters said the cause of Friday's big pileup 30 km from the finish in Metz had been identified.
"A rider tried to take off his over-shoes. It is not his fault, you are packed together like sardines at 70 kph," he told reporters.