Heavy snow and treacherous driving conditions shut down the main highway between Los Angeles and northern California just after 10:30 a.m. Thursday.
The same area was closed on Wednesday for several hours.
Caltrans snowplows raced up and down the freeway through the afternoon, working hard to clear the snow.
One resident said she hadn't seen conditions like this in years.
"I got stuck in Bakersfield last night, I couldn't get home from work and made it over the Grapevine this morning and now I've got to make it over the hill," said Patty Minter of Frazier Park. "This is the worst I've seen it in the 17 years I've lived up here."
Drivers having been dealing with heavy snow, high winds and poor visibility this week due to the storms pounding Southern California.
The Grapevine, also called Tejon Pass, is a 4,100-foot-high road across the Tehachapi Mountains about 50 miles northwest of Los Angeles. It's frequently closed in winter because of fierce winds, snow and black ice.
The Associated Press contributed to this report.