Deaths linked to drugs and drink in Wales have increased by 31% in 10 years, compared with 15% in England.
Figures show 496 people died as a result of drug or alcohol use in 2010 in Wales, against 380 in 2001.
One senior doctor said more preventative action and better access to support services was needed.
Meanwhile, the rate of deaths from avoidable causes remains higher in Wales than in England, despite falling by almost a quarter over the 10 years.
Cardiovascular-related deaths in Wales fell considerably in the period, says the Office for National Statistics.
Dr Charlotte Jones, a GP in Swansea who is deputy chair of the British Medical Association's GP committee, said everybody in the education, health and social sector had to work with the Welsh government and Public Health Wales to improve awareness of the dangers of drink and drugs.
She added: "I do think there is much room for improvement in terms of access to alcohol and drug services.
"There are certain eligibility criteria that are not always right for the individual.
"I think there should be a variety of services available that can engage and meet the requirements of the individual."
She said she did not think the use of drink or drugs was necessarily "any more in our culture than England," but it could come down to greater deprivation.
Clive Wolfendale, chief executive of the North Wales Drug and Alcohol Agency, said the figures should be treated as a "wake-up call" and the Welsh government needed to "up its game" in tackling alcohol-related health issues.
He said: "In my opinion, these figures actually grossly under-estimate deaths, particularly through alcohol.
"Deaths related to liver disease, cancer and heart disease are avoidable through drinking more sensibly.
"Arguments relating to minimum pricing should be seen in this light. The figures show the problem is worse in Wales than in England and it's time the Welsh government maybe followed Scotland's lead."
The drug and alcohol death figures were in a report highlighting the number of avoidable deaths in England and Wales between 2001 and 2010.
Deaths caused by conditions considered avoidable by prevention or good quality health care represented 24% of all deaths registered in England and Wales in 2010.
Martin Blakeborough, chief executive of drugs charity Kaleidoscope, said the figures were "absolutely shocking" but believed the situation may have improved.
"People I've known have died and one is always traumatised by that," he said.
"I would say that in 2001, the spend in England was vastly greater than the spend in Wales and in many ways, Wales has been playing catch-up.
"Over those 10 years, I would hope and I do believe there has been a closing of that gap in the last few years but obviously that won't show in these figures."
The figures show the avoidable death rate per 100,000 population was 205.2 in Wales in 2010, compared to 181.4 in England.
Avoidable death rates in Wales have, however, fallen by 22.4% during the 10-year period, with the rate per 100,000 population at 264.4 in 2001.
A halving in the rate of cardiovascular disease-related deaths was said to be a key driver behind the fall.
Mubeen Bhutta, policy manager at the British Heart Foundation, described the fall as "great news", but it would be premature to say the fight against heart disease was won.
The Welsh government warned against complacency, despite the fall in avoidable death rates.
A Welsh government spokesperson said: "The NHS in Wales has to make fundamental changes to the way it operates if it is to make a vital improvement in quality and safety and avoid becoming an outdated, financially unsustainable system of healthcare.
"While the number of avoidable deaths in Wales has fallen year on year since 2001, we are not complacent. It would be irresponsible and immoral if we were to ignore evidence showing that by making the changes needed, we will reduce the mortality rate.
"Future health services in Wales will need to provide access to high quality, safe and sustainable treatment and care. Together for Health, our five-year plan for the NHS in Wales, sets out what we need to do to achieve that goal."