In the first vote on the issue in 20 years, 330 lawmakers voted against the backbencher-proposed bill while only 118 backed the proposals.
Prime Minister David Cameron was against the bill.
If passed, the Assisted Dying Bill would have allowed doctors to help terminally ill adults diagnosed with less than six months left to live end their life, at the patient's request.
In rival protests outside parliament in London, around 200 campaigners came out in favour of the bill and there were dozens of protesters against it.
Sarah Wootton, chief executive of Dignity in Dying, said the vote showed that MPs were "ridiculously out of touch" with the British public on the issue.
"Suffering will continue as long as MPs turn a blind eye to dying people's wishes," she said.
But Peter Saunders, director of the Care Not Killing campaign, said: "They have done this because they have witnessed mission creep in the tiny number of places that have changed the law to allow assisted suicide and euthanasia."
"While it is not a crime in the UK for someone to take his or her own life, we recognise that it is a tragedy and we, rightly, do all that we can to prevent suicide.
"The assisted dying bill requires us to turn this stance on its head, not merely legitimising suicide, but actively supporting it," they said.
Under the plans, two doctors and a family court judge would have had to assess the patient's prognosis and confirm they were mentally competent and made the decision free from coercion.
In today's vote, MPs were free to vote according to their conscience and the parties did not impose a whip or party line, as would usually be the case.
Assisted suicide is legal in Switzerland, the Netherlands, Belgium and Luxembourg as well as in the US states of Vermont, Oregon and Washington.
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