The crash happened in the area of Mt Vernon Church Road.
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According to the North Carolina State Highway Patrol, a tow truck loaded with a vehicle was headed southbound on Creedmoor Road when it went off the right side of the road. The driver then overcorrected, causing the truck to cross the center line.
The tow truck struck a white van heading northbound. It then spun and also struck a black SUV, also heading northbound.
Emergency workers were seen cutting at least one person, a woman, out of the black SUV and placing her on a stretcher. She was rushed away by ambulance.
Charges are pending against the driver of the tow truck.
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"I was about a half mile back and I saw the smoke," said Grant Mishler, a motorist from Virgilina. "I thought it was much farther ahead."
Mishler said he had to stop on Creedmoor Road because he was towing a lawnmower and didn't want to turn around.
Creedmoor Road closed in Raleigh due to serious crash
"I'm not worried about myself - just really concerned about the people that were involved in this because I saw an SUV leave here that was basically a pile of junk," Mishler said.
Greg Jones, of Cary, was five minutes away from his drop-off when he got stopped.
"There ain't nothing I can do but sit here and wait," Jones said. "Ain't need to go and get all upset. I don't have control of that. If I could turn around I'd turn around, but hey I'm just riding it out."
The road reopened after more than three hours.