Amanda Knox is due to fly home to Seattle after walking free from the Italian prison where she spent four years for Meredith Kercher's murder.
The 24-year-old American won a dramatic courtroom victory when a jury overturned her conviction after a successful appeal.
Knox was sentenced to 26 years in jail in 2009 for the killing that prosecutors said began as a sex game and ended in the stabbing to death of the British student.
Miss Kercher's family, some of whom were in court for the verdict, will meanwhile pick up the pieces and try to come to terms with this new development in the case that has brought them so much pain.
Only one man remains behind bars for the murder now - small-time drug dealer Rudy Guede - after Knox's ex-boyfriend Raffaele Sollecito also won his freedom yesterday.
The Italian 27-year-old had been sentenced to 25 years in prison for what prosecutors said was his part in the gruesome killing. But like Knox, he maintained his innocence, and the climax of the appeal vindicated them both.
Miss Kercher's father, John Kercher, told the Daily Mirror their acquittal was "ludicrous", however.
"It makes a mockery of the original trial," he said. "We are all shocked. We could understand them reducing the sentence, but completely freeing them? Wow."
His opinion seemed to be shared by the huge crowd gathered in the piazza outside the court house in Perugia, the medieval city where the murder took place.
In chaotic scenes that threatened to turn violent at times, hundreds of angry members of the public cried "shame" as news of the verdicts reached them.