Researchers spent more than six years following 8,000 people and found that those taking supplements were just as likely to have developed cancer or heart disease as those who took an identical-looking dummy pill.
And when they were questioned on how healthy they felt, there was hardly any difference between the two groups.
Many users fall into the category of the 'worried well' - healthy adults who believe the pills will insure them against deadly illnesses - according to Catherine Collins, chief dietician at St George's Hospital in London.
"It's the worried well who are taking these pills to try and protect themselves against Alzheimer's disease, heart attacks and strokes," the Daily Mail quoted her as saying.
"But they are wasting their money. This was a large study following people up for a long period of time assessing everything from their mobility and blood pressure to whether they were happy or felt pain," she stated.
Multi-vitamin supplements have become increasingly popular as a quick and easy way of topping up the body's nutrient levels.
But a series of studies have indicated that, for some people, they could actually be harmful.
While the evidence that vitamins can do harm is still limited, the latest study seems to confirm that many people are at the very least taking them unnecessarily.
A team of French researchers, led by experts at Nancy University, tracked 8,112 volunteers who took either a placebo capsule, or one containing vitamin C, vitamin E, beta-carotene, selenium and zinc, every day for just over six years.
They assessed the state of their health at the beginning and end of the trial, taking a quality of life survey designed to measure everything from mobility and pain to vitality and mental health.
When researchers analysed how many in each group had gone on to develop serious illnesses over the years, they found little difference.
In the supplement group, 30.5 per cent of patients had suffered a major health 'event', such as cancer or heart disease. In the placebo group, the rate was 30.4 per cent.
There were 120 cases of cancer in those taking vitamins, compared to 139 in the placebo group, and 65 heart disease cases, against 57 among the dummy pill users.
"The perception that supplementation improves general well-being is not supported by this trial," the researchers concluded.
The findings have been published in the International Journal of Epidemiology.