Oregon State Police said the ambulance was responding to a rollover crash on the northbound side of the freeway near milepost 27 at about 11:00 p.m. Sunday.
OSP said shortly after, two cars traveling at the normal highway speed crashed into the ambulance, sending multiple people to the hospital.
I-5 northbound was shut down during the extended crash investigation.
At least four people were injured, including two paramedics and an Ashland firefighter.
After being shut down for hours, I-5 northbound between Phoenix and Medford was back open at about 6:30 a.m. Monday.
“What could have been a tragedy was miraculously avoided last night. I want to make sure everyone out there knows how important it is to slow down for emergency workers on roadways, particularly at night,” said Ashland Fire Chief Ralph Sartain.