Deaths from paracetamol overdoses fell by 43% in England and Wales in the 11 years after the law on pack sizes was changed, according to a study.
But the number of people taking paracetamol overdoses had not declined, says the Oxford University study published in the BMJ.
In 1998, the government restricted pack sizes in the UK to 32 tablets in pharmacies and 16 in other shops.
Researchers say the figures should not lead to "complacency".
Paracetamol overdoses are a common method of suicide and a frequent cause of liver damage.
Previous studies suggested the decision to restrict the size of packs of paracetamol sold over the counter showed initial benefits in both these areas, but there was no data on the long-term impact.
Using figures from the Office for National Statistics, the Oxford researchers looked at deaths involving paracetamol in people aged 10 years and over between 1993 and 2009.
They found there were 765 fewer deaths after the legislation was introduced in 1998 than would have been predicted based on trends dating back to 1993.
This equated to an average of 17 fewer deaths every three months after 1998.
The study also found that patients registered for a liver transplant because of a paracetamol overdose had reduced by 61% following the legislation. This was equivalent to 482 fewer registrations over 11 years.
More to do
Prof Keith Hawton, lead researcher from the University of Oxford Centre for Suicide Research, said lives had been saved since the change in the law.
"While some of this effect could have been due to improved hospital management of paracetamol overdoses, we believe that this has in large part been due to the introduction of the legislation.
"We are extremely pleased that this measure has had such benefits, but think that more needs to be done to reduce the toll of deaths from this cause."
Despite the reduction in deaths from paracetamol, the study found there had been no decline in overdose cases after 1998.
The study added that additional measures would be needed to reduce the death toll, such as further lowering the limit on tablets in packs, reducing the paracetamol content of the tablets and enforcing the legislation more effectively.
Catherine Johnstone, chief executive of Samaritans said: "When a person is in suicidal crisis, they will often think of a method that is easily available to them.
"It is during this time, we need to make sure that there are no barriers to seeking help aiming to widen the gap between thought and action in the hope that the crisis period will pass before a suicide attempt is made.
"This is the basic reasoning behind the reduction in the numbers of paracetamol pills sold in a pack and it's encouraging to see that legislation can have an effect on reducing suicides.
"The very act of calling an organisation like Samaritans can be sufficient to get a person through a difficult period and the experience of having another human being listen to your problems, in absolute confidence, can give someone the strength to see other choices."
Ged Flynn - from the suicide prevention charity, Papyrus - said the findings support the point that people are less likely to end their lives, if access to harmful things is made harder.
"An example would be, from our point of view, reducing access to information online, which is dangerous to young, vulnerable people."
Paul Farmer, from mental health charity Mind, said that despite the significant impact of paracetamol packaging, there was a bigger issue at stake. The latest statistics showed an overall increase in the number of people taking their own lives since the start of the recession.
"Now more than ever there is urgent need for support, to prevent people with mental health problems ever reaching crisis point.
"We need to see suicide training for GPs, better access to a range of therapies and, crucially, inadequacies in crisis care services must be addressed. People must be able to get the help they need when they need it the most."
A Medicines and Healthcare Products Regulatory Authority spokesperson said: "We welcome the findings of the study and the positive changes that resulted from the pack size restrictions implemented in 1998.
"The MHRA continuously monitors the safety of all marketed medicines and takes action as necessary. For paracetamol, this has included updating warnings to ensure they are well understood and improving the way paracetamol is given to children.
"The benefits associated with using paracetamol far outweigh the risk of serious side effects and we will closely review all options to manage the risks and benefits of medicines."