James Hinchcliffe, James Davison, Oriol Servia and Will Power were all involed in the crash at turn one and have all been ruled out of the race.
Moments earlier Fernando Alonso had been forced out of the race after suffering engine failure.
And shortly after the red flag were out on the track again as the four-car colission wrecked havoc.
All four drivers were unhurt following the crash though.
IndyCar tweeted: MEDICAL UPDATE: @Hinchtown, @12WillPower, @OriolServia, and @JD33Davison checked cleared and released #Indy500 #INDYCAR."
Indy 500: Most spectacular crashes from Indianapolis Sun, May 28, 2017
Express Sport takes a look at some of the spectacular crashes from the Indy 500
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Jay Howard and Scott Dixon collided during the 101st Indy 500
The crash was the final incident after a thrilling day's racing at Indy 500.
Scott Dixon and Jay Howard provided the biggest scare as the former's car was sent flying into the air in a nasty collision.
Later on in the race Buddy Lazier had to be taken to hospital after smashing into the wall at turn two.
Takuma Sato eventually emerged victorious at th101st Indy 500 after 200 laps of racing.
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