Explaining their ruling, the judges said Amanda Knox and her Italian ex-boyfriend, Raffaele Sollecito, killed Meredith Kercher after a violent argument.
Amanda Knox and Raffaele Sollecito were originally convicted of the murder in 2007.
They were acquitted on appeal in 2011, but that ruling was overturned in January.
Amanda Knox, who is currently in the US, was sentenced to 28 years and six months. Her former boyfriend received 25 years.
Both had pleaded not guilty.
Explaining its reasoning on Tuesday, the appeals court in Florence said Meredith Kercher’s wounds indicated multiple aggressors.
The judges said they believe both Amanda Knox and Raffaele Sollecito wielded knives, as another man, Rudy Guede, held the victim down and committed a s**ual assault.
But it was Amanda Knox who “delivered the only mortal blow”, striking Meredith Kercher with a kitchen knife, presiding judge Alessandro Nencini concluded.
The prosecution had originally argued that Meredith Kercher was killed in a s** game that spiraled out of control.
But in its explanation, the appeals court agreed with a later theory that she was killed after a violent quarrel.
It said Amanda Knox and Meredith Kercher had fought over money on the night of the killing.
In a statement on Tuesday, Amanda Knox said the court’s reasoning was “not supported by any credible evidence or logic”.
Both Amanda Knox and Rafafele Sollecito are expected to appeal against the latest decision.
The trial will now go back to Italy’s highest court, the Court of Cassation, which could uphold or overturn the verdict.
If it upholds it, officials are expected to begin the lengthy process to extradite Amanda Knox from the US, where she returned on her release from prison in 2011.
Meanwhile, Rudy Guede is already serving a 16-year prison sentence after being convicted of Meredith Kercher’s murder at an earlier trial.
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