The Edge has performed four songs in the Sistine Chapel to raise awareness for cancer prevention, becoming the first contemporary artist to play at the venue.
The guitarist played for around 200 doctors, researchers and philanthropists as part of a conference at the Vatican on regenerative medicine.
He played acoustic guitar and was backed by a choir of seven Irish teenagers.
He performed Leonard Cohen's If It Be Your Will, and versions of three U2 songs.
The Edge, whose real name is David Evans, lost his father to cancer last month.
He is on the board of several foundations working in aid of cancer prevention.
"When they asked me if I wanted to become the first contemporary artist to play in the Sistine Chapel, I didn't know what to say because usually there's this other guy who sings," he said, referring to U2 front man Bono.
"Being Irish you learn very early that if you want to be asked to come back it's very important to thank the local parish priest for the loan of the hall."
He also thanked Pope Francis and other Vatican officials "for allowing us to use the most beautiful parish hall in the world".
The Edge dedicated his performance of Walk On to Pope Francis, who he described as "the people's Pope".
"He's doing an amazing job and long may he continue," he said.
The Vatican conference was organised by the US-based Stem for Life Foundation to share ideas and treatments on the use of adult stem cells to cure rare diseases.
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