Drugs claimed 230 lives in South Yorkshire over two years, new figures reveal.
The Office for National Statistics has revealed that between 2014 and 2016 there were 6,603 drug-related deaths nationally.
In Sheffield there were 107 deaths - 6.7 per every 100,000 people.
There were 47 drug related deaths recorded in Doncaster, 41 in Rotherham and 35 in Barnsley.
The ONS report shows Blackpool with the highest rate of drug-related deaths in England and Wales for the sixth consecutive year.
There were 79 registered drug poisoning deaths in the seaside town between 2014 and 2016 - 20 for every 100,000 people.
Neath Port Talbot local authority in Wales and Burnley in Lancashire recorded the next highest rates of drug deaths per 100,000 residents.
The figures show that drug poisoning deaths have surged to a new record level, driven in part by a jump in fatalities involving cocaine.
Official statistics show 3,744 deaths involving legal and illegal drugs were registered in England and Wales last year - the highest number since comparable records started in 1993.
Of those, 2,593 - 69 per cent - were classed as drug misuse deaths.
The figures show there were 371 deaths involving cocaine - a rise of 16 per cent on the figure recorded in 2015.
Statisticians identified a rise in the purity of cocaine as one possible explanation for the increase, which has been logged despite estimates of usage remaining broadly steady.
The ONS report cites a warning from the National Crime Agency that there was a 'significant increase' in both crack and powder cocaine purity in 2016, including at user-level.
This 'may partly explain the increase in deaths relating to cocaine', the report says.
A study published earlier this year flagged up 'unprecedented' purity levels for street cocaine.
In contrast to cocaine, deaths linked to heroin and morphine remained stable last year - with 1,209 compared with 1,201 registered in 2015.
There were rises in deaths involving the powerful painkiller fentanyl - from 34 in 2015 to 58 in 2016; paracetamol - from 197 to 219 and new psychoactive substances - from 114 to 123.
The figures have prompted criticism of the Government's drugs policy.
Martin Powell, of the Transform Drug Policy Foundation, described the Home Office's approach as 'scandalous'.
He said: "The Government must accept responsibility for record numbers of people dying from overdoses year after year.
"Other countries value the lives of vulnerable people who use drugs enough to implement and fund many measures proven to save lives, like decriminalising drug users, safer drug consumption rooms and prescribing heroin."
Rosanna O'Connor, of Public Health England, said: "It is tragic that we are still seeing an increase in people dying from drug misuse, particularly among older heroin users.
"Many of these deaths can be explained as the 'Trainspotting' generation, often with poor physical and mental health, sadly losing their battle with long-term addiction to drugs."
She said a large number of heroin deaths are among people not in treatment and called on services to increase their efforts to reach those most at risk.
A Government spokeswoman said: "Any death related to misuse of drugs is a tragedy.
"While drug misuse is lower than 10 years ago, we are absolutely committed to reducing it and the harm it causes.
"That's why last month the Government released a comprehensive new drugs strategy, setting out a balanced approach which brings together police, health, community and global partners to tackle the illicit drug trade, protect the most vulnerable and help those with drug dependency to recover and turn their lives around."