A study shows that a single pill containing four medicine is able to decrease the number of heart attacks and strokes by third.
With blood-thing aspirin, a cholesterol-lowering satin and two drugs to lower blood pressure, the polypill becomes a major lifesaver, reports BBC.
The researchers from Iran and UK said the pills had only cost pennies a day but had a huge impact.
They suggest giving it to everyone over a certain age in poorer countries, where doctors have fewer options and are less able to assess individuals.
Coronary heart disease and stroke are the top two causes of death worldwide, killing more than 15 million people a year.
Smoking, obesity and doing little exercise all increase the risk of an unhealthy heart.
The study, published in the Lancet, was based in more than 100 villages in Iran and about 6,800 people took part.
Half the people were given the polypill and advice on how to improve their lifestyle, with the other half just getting the advice.
After five years there were:
202 major cardiovascular events in the 3,421 people getting the polypill
301 in the 3,417 not getting the pill
At this rate, giving the preventative drug combination to 35 people would prevent one of them developing a serious heart problem over the course of five years.
"We've provided evidence in a developing or middle-income country - and that's a lot of countries - that this is a strategy worth considering," Professor Tom Marshall, from the University of Birmingham, told BBC News.
The polypill led to large reductions in bad cholesterol but had only a slight effect on blood pressure, the study showed.
The drug was given to people over the age of 50 whether they had had a previous heart problem or not.
A third of Britons with high blood pressure were unaware they have the condition
"Given the polypill's affordability, there is considerable potential to improve cardiovascular health and to prevent the world's leading cause of death," said Dr Nizal Sarrafzadegan, of Isfahan University of Medical Sciences, Iran.
The idea of the polypill has been around since 2001 but this is the first major trial to prove its effectiveness.
In the UK and other wealthier countries doctors have the time to assess the needs of individual patients and a wide choice of different drugs, such as statins, to chose from.
"In the UK, the advantages would be more marginal and you would probably want a clinical trial to see any benefits over what is offered at the moment, said Prof Marshall.
The drug is also not licensed in the UK and would be tricky to get approved.
The British Heart Foundation said a third of Britons with high blood pressure were unaware they have the condition.
"This means that the biggest priority in the UK is to identify more people who do not realise they have high blood cholesterol or high blood pressure and to help people prescribed medications to take them as prescribed," the charity said.