Alcohol accounted for the greatest number of drug-related deaths in Ireland between 2004 and 2009.
The latest figures from the Health Research Board show 3,334 people died in the six-year period, with men accounting for 68% of deaths.
More than two-thirds of the deaths were due to poisoning, which included alcohol poisoning.
Heroin-related deaths also increased by 20% in 2009.
Half of all who died were aged 37 years or under with the majority of those who died by poisoning aged between 25 and 44 years.
The number of deaths among drug users that were due to traumatic or medical causes (non-poisoning deaths) rose to 281 in 2009 from 260 in 2008.
The number increased by 81% over the six years, from 155 in 2004 to 281 in 2009.
Of the non-poisoning deaths in 2009, over half (157) were due to trauma.
The number of deaths due to medical causes rose to 124 in 2009 from 111 in 2008, with the main medical cause of death being a cardiac event.
Senior researcher at the HRB Dr Suzi Lyons said they had seen a significant rise in drug-related deaths and deaths among drug users in Ireland over the last six years.
She said: "The inclusion of alcohol-only poisonings in the figures highlights the detrimental impact of alcohol in drug-related deaths, while the rise in the number of deaths where heroin is implicated is also of concern".