REUTERS/Lucy Nicholson
Around two-thirds of these deaths, which averaged at about 10 a day, came from misusing illegal drugs, the ONS said.
Deaths involving heroin or morphine doubled in the last three years to 1,201 in 2015.
This surge is "partly driven by a rise in heroin purity and availability over the last three years," ONS Vanessa Fearn, said.
"Age is also a factor in the record levels of drug deaths, as heroin users are getting older and they often have other conditions, such as lung disease and hepatitis, that make them particularly vulnerable," said Fearn.
Here's the chart showing how heroin flows across the world:
UN World Drug Report 2016
Deaths from cocaine use hit an all-time high of 320 in 2015 - up from 247 in 2014.
In accounting for its data, the ONS said that "over half of all drug poisoning deaths involve more than one drug and/or alcohol, and it is not possible to tell which substance was primarily responsible for the death."
Within England, the North East had the highest mortality rate from drug misuse in 2015 for the third year running (68.2 deaths per million population), while the East Midlands had the lowest (29.8 deaths per million).