Results were based on nearly 640,000 adults with an average age of between 44 and 71 years old, tracked over a combined total of 6.5 million years.
In total, they studies included more than 28,000 deaths, nearly 10,000 cases of cardiovascular diseases and nearly 24,000 cases of diabetes.
By combining and standardising the results, researchers found a daily serving of butter - 14g or roughly one tablespoon - was associated with a 1 per cent higher risk of death.
Butter consumption had 'no significant association' with any type of cardiovascular disease, including coronary heart disease and stroke.
A smaller sample of results indicated a daily serving of butter was associated with a 4 per cent lower risk of type 2 diabetes - although researchers said this needed further investigation.
The paper said: 'Together, these findings suggest relatively small or neutral associations of butter consumption with long-term health... A major focus on eating more or less butter, by itself, may not be linked to large differences in mortality, cardiovascular disease or diabetes.
'In sum, our findings do not support a need for major emphasis in dietary guidelines on butter consumption, in comparison to other better established dietary priorities.'
Senior author Dr Dariush Mozaffarian added: "Our results suggest that butter should neither be demonized nor considered 'back' as a route to good health."
Study researcher Dr Laura Pimpin, now at the UK Health Forum, said: "Even though people who eat more butter generally have worse diets and lifestyles, it seemed to be pretty neutral overall.
"This suggests that butter may be a 'middle-of-the-road' food: a more healthful choice than sugar or starch, such as the white bread or potato on which butter is commonly spread and which have been linked to higher risk of diabetes and cardiovascular disease; and a worse choice than many margarines and cooking oils - those rich in healthy fats such as soybean, canola, flaxseed, and extra virgin olive oils."
Commenting on the research, cardiologist and National Obesity Forum advisor Dr Aseem Malhotra said: 'This high quality study clearly reveals that decades of demonising butter has been a huge mistake.
"I follow the advice I give to my patients which is providing you cut the consumption of sugar and other refined carbohydrates the regular consumption of butter can be very much part of a healthy diet."
But Professor Pete Wilde, of the Institute of Food Research, warned the study was not a "carte blanche to consume large amounts of butter".
And Tracy Parker, of the British Heart Foundation, added: 'While the findings of this review indicate a small or neutral association between butter consumption and increased cardiovascular risk, it does not give us the green light to start eating more butter.
"More investigations are needed into the effects of saturated fat.
"What we do know is fat is just one element of our diet. There are many factors which cause cardiovascular disease and no single food or nutrient is solely responsible for this.
"To protect your heart health we would recommend a balanced Mediterranean style diet rich in fruit, vegetables and pulses."
Cardiovascular diseases are conditions such as heart disease and strokes which involve a reduced blood flow to the heart, brain or body due to a blockage or narrowing of the arteries.
And across the globe, heart disease and stroke are the leading causes of death, according to the American Heart Association.
High blood pressure, high cholesterol, smoking, being overweight and a lack of exercise are all risk factors.
