Yet hard proof remains elusive, and nine years on, tracking down anyone who might have slipped minuscule amounts of the lethal substance into Arafat's food or drink could be difficult.
A new investigation could also prove embarrassing - and not just for Israel, which the Palestinians have long accused of poisoning their leader and which has denied any role.
The Palestinians themselves could come under renewed scrutiny, since Arafat was holed up in his Israeli-besieged West Bank compound in the months before his death, surrounded by advisers, staff and bodyguards.
Arafat died at a French military hospital on November 11, 2004, at age 75, a month after suddenly falling violently ill at his compound. At the time, French doctors said he died of a stroke and had a blood-clotting problem, but records were inconclusive about what caused that condition.
The Swiss scientists said that they found elevated traces of polonium-210 and lead in Arafat's remains that could not have occurred naturally, and that the timeframe of Arafat's illness and death was consistent with poisoning from ingesting polonium.
"Our results reasonably support the poisoning theory," Francois Bochud, director of Switzerland's Institute of Radiation Physics, which carried out the investigation, said at a news conference.
Bochud and Patrice Mangin, director of the Lausanne University Hospital's forensics center, said they tested and ruled out innocent explanations, such as accidental poisoning.
"I think we can eliminate this possibility because, as you can imagine, you cannot find polonium everywhere. It's a very rare toxic substance," Mangin told The Associated Press.
Palestinian officials, including Arafat's successor, Palestinian President Mahmoud Abbas, had no comment on the substance of the report but promised a continued investigation.
The findings are certain to revive Palestinian allegations against Israel, a nuclear power. Polonium can be a byproduct of the chemical processing of uranium, but usually is made artificially in a nuclear reactor or a particle accelerator.
Arafat's widow, Suha, called on the Palestinian leadership to seek justice for her husband, saying, "It's clear this is a crime."
Speaking by phone from the Qatari capital Doha, she did not mention Israel but argued that only countries with nuclear capabilities have access to polonium.
In another interview later Thursday, she described her husband's death as a "political assassination" and "the crime of the century" and called the new testing conclusive for poisoning. She said she couldn't predict who was behind the death, but she added, "Whoever did this crime is a coward."
Israel has repeatedly denied a role in Arafat's death and did so again Thursday. Paul Hirschson, a Foreign Ministry official, dismissed the claim as "hogwash."
"We couldn't be bothered to" kill him, Hirschson said. "If anyone remembers the political reality at the time, Arafat was completely isolated. His own people were barely speaking to him. There's no logical reason for Israel to have wanted to do something like this."
In his final years, Arafat was being accused by Israel and the US of condoning and even encouraging Palestinian attacks against Israelis instead of working for a peace deal. In late 2004, Israeli tanks no longer surrounded his compound, but Arafat was afraid to leave for fear of not being allowed to return.
Shortly after his death, the Palestinians launched their own investigation, questioning dozens of people in Arafat's compound, including staff, bodyguards and officials, but no suspects emerged.
Security around Arafat was easily breached toward the end of his life. Aides have described him as impulsive, unable to resist tasting gifts of chocolate or trying out medicines brought by visitors from abroad.
The investigation was dormant until the satellite TV station Al-Jazeera persuaded Arafat's widow last year to hand over a bag with her husband's underwear, headscarves and other belongings. After finding traces of polonium in biological stains on the clothing, investigators dug up his grave in his Ramallah compound earlier this year to take bone and soil samples.
Investigators noted Thursday that they could not account for the chain of custody of the items that were in the bag, leaving open the possibility of tampering.
However, the latest findings are largely based on Arafat's remains and burial soil, and in this case, tampering appears highly improbable, Bochud said.
"I think this can really be ruled out because it was really difficult to access the body," he said. "When we opened the tomb, we were all together."
Polonium-210 is the same substance that killed KGB agent-turned-Kremlin critic Alexander Litvinenko in London in 2006.
"It's quite difficult to understand why (Arafat) might have had any polonium, if he was just in his headquarters in Ramallah," said Alastair Hay, a professor of environmental toxicology at the University of Leeds who was not involved in the investigation.
"He wasn't somebody who was moving in and out of atomic energy plants or dealing with radioactive isotopes."