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One of the world's richest men, Mr Hughes was best known as a movie magnate, aviation pioneer and businessman.
He had spent the last 20 years out of the public eye living as a recluse in hotel penthouses around the world.
He died on a plane flying him from Acapulco, Mexico, to Houston, in Texas, for medical treatment at the Methodist Hospital.
There has been much speculation in the media about his lifestyle.
Some reports say he had a phobia of germs that kept him out of contact with the outside world - in darkened rooms, eating little and wearing nothing for fear of catching a disease.
He is believed to have lived on the top floor of the Xanadu Princess Hotel in Freeport, Bahamas, since 1973.
Before that he had spent a few months in a penthouse at London's Inn on the Park and some years in Managua, Nicaragua.
From 1966 until 1970 he occupied the top floor of the Desert Inn in Las Vegas where he bought several properties, casinos and mining claims.
Films and flying
Howard Robard Hughes was born in Houston, Texas, in 1905. He was just 17 when he took over his father's Hughes Tool Company that patented a drill bit used on most of the world's oil drills.
The company became the foundation of his fortune which now stands at around $2 billion.
He used his wealth to become a Hollywood producer he made such films as Hell's Angels (1930), Scarface (1932), and The Outlaw (1941).
During this time he "discovered" actresses Jean Harlow and Jane Russell and was reported to have had affairs with Katharine Hepburn, Bette Davis, Gene Tierney and Ava Gardner.
He married actress Jean Peters in 1957 but they divorced in 1971.
Howard Hughes had a passion for aviation and founded the Hughes Aircraft Company and even set a world speed record flying his own plane in 1935. Three years later he flew around the world in record time.
His company designed and constructed airplanes for commercial and military use, and during the 1940s and 1950s a subsidiary, Hughes Electronics, was one of the major suppliers of weapons to the US Air Force and Navy.
He designed several aircraft himself including the massive eight-engine Spruce Goose, made mainly out of birch and designed to carry 700 passengers.
It had been commissioned by the US government for use in World War II, but was not completed until after the war. It flew only once, with Mr Hughes at the controls, in 1947.
That same year the billionaire aviator was nearly killed in an air crash while testing one of his own planes.
In the early 1950s Mr Hughes gave up control of the Hughes Aircraft Company to an independent executive board following senior executive departures.
In 1953 he donated all his stock in the company to his new Howard Hughes Medical Institute in Delaware founded for biomedical research.
Mr Hughes was embroiled in several legal lawsuits against him by aggrieved employees. The most costly involved TransWorld Airlines (TWA) of which he had been a majority shareholder since 1939. He was forced to sell up in 1966 after a wrangle over his failure to invest in jets for the fleet.
After years of neglect, the body of Howard Hughes was almost unrecognisable and the FBI had to take fingerprints to identify it.
An autopsy concluded he had died of kidney failure - there were also large amounts of codeine and Vallium found in his bloodstream.
He was buried in the Glenwood Cemetery in Houston on 7 April 1976.
In the days following his death there was a frantic search for the billionaire's will.
A handwritten will was discovered in the headquarters of the Mormon Church in Salt Lake City.
It became known as the "Mormon will" and in it Hughes seems to have left one-16th of his $2bn fortune to a Utah service station owner called Melvin Dummar.
Mr Dummar said that in 1967 he had been driving along a desert road in Nevada and had given a lift to a dishevelled man who told him later that he was the billionaire Howard Hughes.
A Nevada court ruled the will was a forgery and that Hughes had died intestate. His billions were left to 22 of his cousins.
The extraordinary story of the Mormon will was made into a film called Melvin and Howard in 1980.
Director Martin Scorsese made a film about Howard Hughes called The Aviator in 2004.
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