The study by CQ Press found St. Louis had 2,070.1 violent crimes per 100,000 residents, compared with a national average of 429.4. That helped St. Louis beat out Camden, which topped last year's list and was the most dangerous city for 2003 and 2004.
Detroit, Flint, Mich., and Oakland, Calif., rounded out the top five. For the second straight year, the safest city with more than 75,000 residents was Colonie, N.Y.
The annual rankings are based on population figures and crime data compiled by the FBI. Some criminologists question the findings, saying the methodology is unfair.
Greg Scarbro, unit chief of the FBI's Uniform Crime Reporting Program, said the FBI also discourages using the data for these types of rankings.
Kara Bowlin, spokeswoman for St. Louis Mayor Francis Slay, said the city actually has been getting safer over the last few years. She said crime in St. Louis has gone down each year since 2007, and so far in 2010, St. Louis crime is down 7 percent.
Erica Van Ross, spokeswoman for the St. Louis Police Department, called the rankings irresponsible.
"Crime is based on a variety of factors. It's based on geography, it's based on poverty, it's based on the economy," Van Ross said.
"That is not to say that urban cities don't have challenges, because we do," Van Ross said. "But it's that it's irresponsible to use the data in this way."