BOWLING GREEN, Va.—Federal regulators have shut down East Coast discount bus service SkyExpress after a crash in Virginia that killed four people and sent more than 50 others to hospitals.

The U.S. Department of Transportation issued an unsatisfactory safety rating and prohibited SkyExpress, of Charlotte, N.C., from operating interstate transportation. It said in a statement Tuesday the bus company violated multiple federal safety regulations.

A SkyExpress bus headed to New York City swerved off northbound Interstate 95 early Tuesday, hit an embankment and overturned about 30 miles north of Richmond.

The driver, Kin Yiu Cheung, was charged with reckless driving, and police say his fatigue was a factor in the crash. Federal documents show the company has a poor safety record.

Gail Parenteau, a spokeswoman for SkyExpress, confirmed the so-called out-of-service order issued by the Transportation Department's Federal Motor Carrier Safety Administration but said the company had suspended service on almost all of its buses as soon as it learned of the accident.

Transportation Department spokeswoman Candice Tolliver said the ban is indefinite.

Over the last two years, the company has been involved in several accidents, according to federal records. It also has been cited for 46 violations of drivers being fatigued over that same time.

SkyExpress offers $30 bus trips between New York and 15 cities in North Carolina, Virginia, South Carolina, Georgia and Florida. It also goes to Washington, D.C.

The carrier is part of an industry of inexpensive buses on the highways of the East Coast that offer cheap fares, convenient routes and in some cases free wireless Internet. The industry is in the fifth year of a boom, but fatal accidents have prompted calls for tougher federal regulation.

The bus departed Greensboro, N.C., on Monday night and was headed to Chinatown in New York City with 59 people aboard. Mr. Cheung, 37, of Flushing, N.Y., was being held in an area jail on $3,000 bond, and the National Transportation Safety Board was investigating.

According to Federal Motor Carrier Safety Administration records, SkyExpress Inc. buses have been involved in four crashes, with an injury or fatality—it didn't specify which—during the two-year period that ended May 20.

The company offered its condolences to the families of the four women killed and said it would cooperate fully in the investigation.

"This is the first serious accident" involving SkyExpress buses, the company said in a statement. "The bus driver has never before been involved in an accident."

The company's drivers have been cited for 17 unsafe-driving violations, including eight for speeding, since 2009, according to a report by the Federal Motor Carrier Safety Administration. It received a 62.9% rating, meaning it performed worse than nearly 63% of comparable transportation companies.

Other recent crashes, including one involving another company in March that killed 15 people returning to Chinatown from a Connecticut casino, demonstrate that the bus industry won't take essential steps to protect passengers' safety unless required by the government, the Senate sponsor of a bipartisan bus-safety bill said.

"How many deaths do we have to have before the bus companies are going to start saying, 'Maybe we don't need more time. Maybe we should start doing something about this?' with or without the government telling them to," Sen. Sherrod Brown (D., Ohio) said. "Sometimes they need government mandates."

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