The company is poised to enter the UK, having last month snapped up the fashionable site inhabited for 135 years by Barkers department store on Kensington High Street. Will the British bite?
"First of all I expect we will be attacked and there will be a certain amount of negative publicity. Americans are not perceived as very food savvy, and [people will think] it is another big corporation," said Mr Mackey, who set up a precursor to Whole Foods when he dropped out of a philosophy course at Texas University 27 years ago and joined a vegetarian co-op, thinking he might meet attractive women.
But he is confident that any negative reaction will soon disperse and that the 75,000-ft store will elbow its way into Britain's crowded supermarket sector when it opens in early 2007. "It will be the best store we've ever opened and no one is doing what Whole Foods plans to do," added the 52-year-old, whose business attire is shorts and trainers.
If Mr Mackey delivers on his pledge, the store might not be able to get rid of shoppers. Those in charge of Whole Foods' flagship outlet which opened in Austin in March report they see customers wandering around for hours - not because they cannot locate the eggs, but because they cannot pull themselves away from what is something of a foodie's paradise.
There are ovens baking fresh bread and beautifully staked fruit and vegetables. There are stands of luxury chocolate and spacious areas with salad bars and other mini-restaurants. The store, which makes a point of selling local produce as well as exotic goods, makes its own sausages and does its own meat smoking.
Whole Foods' winning formula comes from the fact that it is a broadminded kind of health food store, its creator says.
Mr Mackey may have fallen into vegetarianism because it was the "hip and cool" thing to do in the 1970s, but he has become increasingly committed to the way of life and follows an almost completely vegan diet. (The exceptions are eggs laid by his own chickens which roam free at his property outside Austin, and goats cheese made by a local farmer who - Mr Mackey has ensured on a personal visit - "treats the animals very well"). But he recognises that not all of its customers have such strong views about the ethics of what they eat, or its health content.
"I don't think ice cream is a healthy product, it is full of fat and sugar. But we made a decision a long time ago that we weren't only going to sell products that were good for people because we would end up being an organic produce stand."
Such is Mr Mackey's success and his rise to prominence in the vegetarian movement that he has become a lightning rod for allegations that he is something of a hypocrite. Some vegan friends have objected to the fact that Whole Foods sells meat, fish and cheese, all the more popular since the Atkins diet rose to prominence in the US.
"Their message is 'You either ought to convert your stores to be vegan stores or you should resign'. It is easy to be a saint on a mountain top. If I tried to do that I would be fired. If I were to leave, the person who took my place would undoubtedly not have the same concern about animal well-being as I do. So does it really help the animals?"
Whole Foods does have strict guidelines about making sure its food either meets national organic standards, which ban harmful pesticides and other chemicals, or is as close to its natural state as possible. Mr Mackey obviously does believe strongly in the ethical side of the business. The meat sold by Whole Foods, which Mr Mackey prefers to call "dead animals", has to have been treated in a compassionate way which far exceed most organic standards.
Whole Foods tries to operate its business in a way which is kind to the environment, with several stores using solar and wind power. It focuses on cutting packaging, and customers are asked whether they want a plastic or paper bag or no bag at all. Workers are paid for the community work they do, and there is a cap on anyone - including Mr Mackey - being paid more than 14 times the group's average salary. "There is no inherent reason why business cannot be ethical, socially responsible and profitable. In fact all businesses should be ethical and socially responsible and profitable."
Investors certainly cannot complain. Profits as a percentage of sales are the highest of all retailers in the Fortune 500 index, including the world's largest retailer, Wal-Mart. The company is expanding at such a rate that it is doubling in size every three and a half years. Ithas 172 outlets, ranging from smaller stores mainly offering prepared food to full-blown gourmet supermarkets.
In the US, Whole Foods' presence is not just on its traditionally liberal east and west coasts, where consumers are most susceptible to its virtuous and luxurious offerings, but also in conservative places such as Kansas and Georgia. As a first footstep into the UK last year, it bought the small chain Fresh & Wild.
Whole Foods shares have risen from their float price of $4.25 in 1992 to $129 and it has a market value of $8.7bn (£4.9bn). It notched up $137m in profits last year.
Some say such healthy profits are generated by charging exorbitant prices, and the company has attracted the nickname "Whole pay check". Mr Mackey is unrepentant. "People say they want the highest-quality food and they support local production and they want organic and they want food to be fresher. You can't have it both ways. If you want the highest quality, it costs more. It is like complaining that a BMW is more expensive than a Hyundai. Yes, but you're getting a better car."
Others say its dominance in the health-food market makes it the "Wheatgerm Wal-Mart". Mr Mackey rejects this. But, just as the discount retailer is famous for having created its own culture, Mr Mackey has developed a corporate ethos, albeit one where everyone is called a "team member" and head office employees greet each other like friends.
Despite the relaxed exterior, Mr Mackey has far-reaching ambitions, and Wall Street has likened his brand to that of Apple and Starbucks. "[Those] are lifestyle brands and have a certain committed customer that I think Whole Foods has. They're similar in that all three are perceived as innovative, kind of hip, quality products. I hope that some day Whole Foods is as well-known as Apple and Starbucks. We're certainly not there yet."
Position: Chairman and chief executive
Pay: $342,000 (£192,000) plus $118,000 bonus. Mr Mackey also owns 1 per cent of Whole Foods' shares. The company has a market value of $8.7bn
Family: Married, no children
Hobbies: Hiking and reading