The cause of death was "acute intoxication by the combined effects of oxycodone, hydrocodone, diazepam, temazepam, alprazolam and doxylamine," spokeswoman Ellen Borakove said in a statement.
The drugs are the generic names for the painkiller OxyContin, the anti-anxiety drugs Valium and Xanax, and the sleep aids Restoril and Unisom. Hydrocodone is another name for ibuprofen.
Borakove wouldn't say what concentrations of each drug were found in Ledger's blood, or whether one drug played a greater part than another in causing his death.
"What you're looking at here is the cumulative effects of these medications together," she said.
The ruling comes two weeks after the 28-year-old Australian-born actor was found dead in the bed of his rented SoHo apartment. Police found bottles of six types of prescription drugs, including sleeping pills and anti-anxiety medication, in his bedroom and bathroom.
Ledger was discovered by his masseuse on Jan. 22 after she arrived for an appointment that afternoon. She entered his bedroom to set up for the massage and found him unresponsive, and proceeded to call Mary-Kate Olsen three times over the next 9 minutes before dialing 911. Ledger had been dead for some time, and police say no foul play occurred.
Ledger, nominated for an Oscar for his role in "Brokeback Mountain," had returned to New York from London days before his death, where he had been filming a $30 million Terry Gilliam film. He said in a November interview that his most recent completed roles in the Batman movie "The Dark Night" and Bob Dylan biopic "I'm Not There" had taken a toll, saying he couldn't sleep.
"Last week I probably slept an average of two hours a night," Ledger told The New York Times. "I couldn't stop thinking. My body was exhausted, and my mind was still going." He said he had taken two Ambien pills, which only gave him an hour of sleep.
Ledger's family returned to the actor's hometown of Perth, Australia on Tuesday to prepare for his funeral. Arrangements were private.
In a statement released through Ledger's publicist, Ledger's father, Kim, said Wednesday: "While no medications were taken in excess, we learned today the combination of doctor-prescribed drugs proved lethal for our boy. Heath's accidental death serves as a caution to the hidden dangers of combining prescription medication, even at low dosage."