The increase in numbers saw 121 people lose their lives as a direct result of drug abuse in 2012. That is up from 117 in 2011 and 94 in 2010.
However, the figures show the number of drug-related deaths has fallen from the peak of 135 in 2009.
Dr Roy Robertson, from the National Forum on Drug-related Deaths, said: "It is always disappointing to see the depressing loss of life from drug related causes.
"These statistics will help us to review what more can be done by a range of partners and agencies across the country to reduce the risk of drug deaths.
"Scotland should be proud of its national Naloxone programme which is evolving steadily to ensure protection of those most at risk of overdose.
"The Forum will undertake further scrutiny and discussion of the details and implications of today's figures and offer more detailed analysis and advice to the Scottish Government."
Across Scotland, drug-related deaths have fallen slightly, but the figure is the second-highest on record.
There were 581 deaths in 2012 - three fewer than in 2011, according to the General Register Office for Scotland.
The figures also showed a third of deaths - 34% - were among people aged 35-44.
Community Safety Minister, Roseanna Cunningham, said: "We must recognise that these figures published today represent 581 loved ones lost by friends and families across Scotland and each of these deaths is a tragedy.
"The Scottish Government is dealing with a legacy of drug misuse which stretches back decades. This Government believes that recovery from drug addiction is possible.
"Since 2007, we have invested over £194 million in front line drug services and support, with £30.3m invested this year alone."
For the first time, deaths where "legal highs" were implicated have been included in the report.
In 2012, there were 47 drug deaths where legal highs were present, and five cases where they were the only drug present.
Ms Cunningham added: "For the first time, the National Records of Scotland report shows drug deaths where so called legal highs were found in the body.
"While the classification of drugs is a reserved matter, we very much recognise the challenges posed by New Psychoactive Substances, also known as legal highs."