At least 23 people were killed. The driver is among 18 people hospitalized. Nine of those hospitalized are in critical or guarded condition.
A witness, Margaret Messore, said, "It was horrible, it was horrible. The front of the bus was all crashed in. People were hanging out and crying for help, so my husband started breaking windows to get people out."
New Orleans has never seen a highway accident this bad.
Mayor Marc Morial said, "There were many, many good samaritans on the road, who when they saw what happened didn't hesitate to stop and help."
The injured were taken to four area hospitals, and the local trauma unit went on full alert.
Jerry Romig, spokesman for Charity Hospital, said "We're not sure how many we're treating here are going to make it. We've got some very, very badly injured people, and the fact that they're elderly doesn't help us at all."
The driver told hospital staff his last memory was swerving to avoid a car that cut him off. The impact of the crash was so powerful that it took rescuers four hours to remove all the bodies.
Authorities said the accident happened shortly before 9 a.m. as the bus was headed for a casino on Mississippi's Gulf Coast.
The bus, traveling eastbound on Interstate 610, swerved from the left lane into the right lane, then crashed into an embankment at a tunnel for golf carts at the City Park course, police said.
"The bus narrowly missed hitting several other vehicles," police spokesman Joe Narcisse said.
It then came to rest on a grassy area along the highway, which passes through a residential section of the city.
The front of the bus was so crumpled that its front wheels were two feet off the ground. Rescue squads had to brace the bus with timbers and use ladders to reach its windows.
Those aboard included members of an informal gambling club, many of them elderly, some in their 80s. George Tassin said eight members of his family, mostly women on a Mother's Day trip, were on the bus.
Tassin's wife, daughter and an aunt were among the injured, he said as he waited outside the hospital where they were taken.
He said his aunt was making her first trip since the recent death of her husband.
"My aunt finally decided to go this one time and this happened," he said.
Four gambling charter buses crashed in New Jersey en route to Atlantic City in late December and early January. One crash on Christmas Eve killed eight people and injured 15 others.
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