San Antonio police said the accident happened just before midnight Sunday on Loop 1604 near Judson Road.
A woman driving an SUV pulling a trailer lost control of the vehicle when a tire blew.
Witnesses told police the trailer was swaying back and forth before it broke free from the SUV.
The SUV rolled over the median and into oncoming traffic. It was hit by two cars and another car clipped one of the those cars.
The woman driving the SUV was taken to SAMMC in critical condition. She was later downgraded to stable condition.
Several eastbound and westbound lanes of Loop 1604 were closed while crews cleared the accident.
Two other drivers were taken to the hospital with minor injuries.