The toll rose by 61 percent during that period, it said.
The report by the Centers for Disease Control and Prevention said there were 2,905 prescription drug overdose deaths in 2009 compared with 1,804 in 2003, the South Florida Sun Sentinel reported Thursday.
The issue of fatal overdoses has led to a number of new laws in Florida in the past three years, the newspaper said.
The most recent went into effect July 1, requiring pain doctors and clinics to start using new counterfeit-proof prescription pads for addictive drugs.
For every 100,000 Floridians, there were 13.4 deaths from prescription drugs in 2009 compared with 7.3 in 2003, an increase of 84.2 percent, the report said.
The death rate from illegal drugs was down 21 percent.
There were 3.4 deaths per 100,000 Floridians in 2009 from heroin, cocaine and other drugs, compared with 4.3 per 100,000 in 2003.