It happened just before eight Saturday night on Highway 145 near Road 208.
The Highway Patrol says a man driving a Honda Civic was heading west on Highway 145 at speeds of about 70 miles per hour.
The Civic crossed the center divider and into oncoming traffic.
It clipped a GMC Canyon, then crashed head-on into a Honda Accord.
Two people in the Honda Accord were killed and are identified as a man and a woman from Firebaugh.
A third person in the Accord, a woman from Firebaugh remains hospitalized.
The driver of the Honda Civic, 23- year old Madera man was killed.
The highway patrol says alcohol or drugs may have played a role in the crash.