He was the punk poet of rock ' n' roll who profoundly influenced generations of musicians as leader of the Velvet Underground and remained a vital solo performer for decades after.
Reed died in Southampton, New York, of an ailment related to his recent liver transplant, according to his literary agent, Andrew Wylie, who added that the star had been in frail health for months.
Reed shared a home in Southampton with his wife and fellow musician Laurie Anderson, whom he married in 2008.
Reed never approached the commercial success of such superstars as the Beatles and Bob Dylan, but no songwriter to emerge after Dylan so radically expanded the territory of rock lyrics.
Indie rock essentially began in the 1960s with Reed and the Velvets; the punk, New Wave and alternative rock movements of the 1970s, '80s and '90s were all indebted to Reed, whose songs were covered by R.E.M., Nirvana, Patti Smith and countless others.
"The first Velvet Underground record sold 30,000 copies in the first five years," Brian Eno, who produced albums by Roxy Music and Talking Heads among others, once said. "I think everyone who bought one of those 30,000 copies started a band!"
Reed's trademarks were a monotone of surprising emotional range and power; slashing, grinding guitar; and lyrics that were complex, yet conversational, designed to make you feel as if Reed were seated next to you.
He had one top 20 hit, Walk On the Wild Side, and many other songs that became standards among his admirers, from Heroin and Sweet Jane to Pale Blue Eyes and All Tomorrow's Parties.
An outlaw in his early years, Reed would eventually perform at the White House, have his writing published in The New Yorker, be featured by the Public Broadcasting Service in an American Masters documentary and win a Grammy in 1999 for Best Long Form Music Video.
The Velvet Underground was inducted into the Rock and Roll of Fame in 1996 and their landmark debut album, The Velvet Underground & Nico, was added to the Library of Congress' registry in 2006.
Reed called one song Growing Up in Public and his career was an ongoing exhibit of how any subject could be set to rock music - the death of a parent (Standing On Ceremony), Aids (The Halloween Parade), some favourite movies and plays (Doin' the Things That We Want To), racism (I Want to be Black) and the electroshock therapy he received as a teen (Kill Your Sons).
He was one of rock's archetypal tough guys, but he grew up middle class - an accountant's son raised on Long Island, east of New York City.
Reed was born to be a suburban dropout. He hated school, loved rock 'n' roll, fought with his parents and attacked them in song for forcing him to undergo electroshock therapy as a supposed "cure" for being bisexual. "Families that live out in the suburbs often make each other cry," he later wrote.
Reed moved to New York City after college and travelled in the pop and art worlds, working as a house songwriter at the low-budget Pickwick Records and putting in late hours in downtown clubs. One of his Pickwick songs, the dance parody The Ostrich,was considered commercial enough to record.
Fellow studio musicians included a Welsh-born viola player, John Cale, with whom Reed soon performed in such makeshift groups as the Warlocks and the Primitives.
They were joined by a friend of Reed's from Syracuse, guitarist-bassist Sterling Morrison; and by an acquaintance of Morrison's, drummer Maureen Tucker, who tapped out simple, hypnotic rhythms while playing standing up.
They renamed themselves the Velvet Underground after a Michael Leigh book about the sexual subculture.
By the mid-1960s, they were rehearsing at Warhol's "Factory," a meeting ground of art, music, orgies, drug parties and screen tests for films that ended up being projected onto the band while it performed, part of what Warhol called the Floating Plastic Inevitable.
The Velvets said everything other bands were forbidden to say and some things other bands never imagined.
Reed wrote some of rock's most explicit lyrics about drugs (Heroin, 'Waiting for My Man), sadomasochism (Venus in Furs) and prostitution (There She Goes Again).
The mainstream press, still seeking a handle on the Beatles and the Rolling Stones, was thrown entirely by the Velvet Underground. The New York Times at first could not find the words, calling the Velvets "Warhol's jazz band" in a January 1966 story and "a combination of rock 'n' roll and Egyptian belly-dance music" just days later.
A storm cloud over 1967's Summer of Love, The Velvet Underground featured a now-iconic Warhol drawing of a (peelable) banana on the cover and proved an uncanny musical extension of Warhol's blank-faced aura.
Reed made just three more albums with the Velvet Underground before leaving in 1970. Cale was pushed out by Reed in 1968 (they had a long history of animosity) and was replaced by Doug Yule.
Their sound turned more accessible, and the final album with Reed, Loaded, included two upbeat musical anthems, Rock and Roll and Sweet Jane.
He lived many lives in the '70s, initially moving back home and working at his father's office, then competing with Keith Richards as the rock star most likely to die.
He binged on drugs and alcohol, gained weight, lost even more his albums in the '70s were alternately praised as daring experiments or mocked as embarrassing failures, whether the ambitious song suite Berlin or the wholly experimental Metal Machine Music, an hour of electronic feedback.
But in the 1980s, he kicked drugs and released a series of acclaimed albums, including The Blue Mask, 'Legendary Hearts and New Sensations.He played some reunion shows with the Velvet Underground and in 1990 teamed with Cale for Drella, a spare tribute to Warhol.
He continued to receive strong reviews in the 1990s and after for such albums as Set the Twilight Reeling and Ecstasy, and he continued to test new ground, whether a 2002 concept album about Edgar Allan Poe, The Raven, or a 2011 collaboration with Metallica.
What are your favourite memories of Reed? What's your favourite song? Have you ever seen him live and what are your thoughts about him in general?
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