D'Virgilio was the drummer in Spock's Beard since the band began in the early 1990s. After Neal Morse left in 2002, D'Virgilio took over on lead vocals and subsequently recorded four albums, Feel Euphoria, Octane, the self-titled Spock's Beard, and X, prior to his departure in 2011.
In 1994, D'Virgilio joined Kevin Gilbert's reformed band Giraffe for a one-off performance of the Genesis piece "The Lamb Lies Down on Broadway" at Progfest '94. In 1995, he performed drums as part of Gilbert's touring band, Thud, which recorded a live album, Live at the Troubadour, released in 1999. After Gilbert's death in 1996, D'Virgilio was asked by Gilbert's estate to complete his second solo album, The Shaming of the True, based on the extant tapes and Gilbert's notes. Shaming was released posthumously in 2000 and has D'Virgilio on many tracks contributing drums, percussion, bass, guitar, keyboards and backing vocals. In November 2002, D'Virgilio headlined Progwest in Claremont, California and played the entire The Shaming of the True album live in a band consisting of other friends and colleagues of Gilbert's. In 2008, video tapes of the Troubadour concert were uncovered for the first time, leading to a DVD, entitled Welcome to Joytown – Thud Live at The Troubadour, released in 2009.
A lifelong fan of the progressive rock band Genesis, D'Virgilio was given an opportunity by the band to replace Phil Collins on drums for their 1997 album Calling All Stations. D'Virgilio split percussion duties with Nir Zidkyahu during work on the album.
D'Virgilio was a full member of the Mike Keneally Band from 2001 to 2004, playing on the tour supporting Keneally's 2000 album Dancing and later providing drums and vocals on the 2004 album Dog, as can be seen on the DVD included as part of the Dog Special Edition in both live as well as "making-of" studio footage. Previous Keneally drummer Joe Travers took D'Virgilio's place in the band for the subsequent Guitar Therapy tour.
D'Virgilio's first solo album, Karma, was recorded in 2001 at Kevin Gilbert's former studio, Lawnmower and Garden Supplies Studio, in Pasadena. The album included performances by Mike Keneally and Bryan Beller, D'Virgilio's bandmates in The Mike Keneally Band. D'Virgilio also served as the chief engineer on Beller's solo album View, recorded at the same studio as Karma.
D'Virgilio filled in for Mark Zonder on Fates Warning's summer tour with Dream Theater and Queensrÿche in 2003. Zonder's prior commitments prevented him from taking part in the tour, and he ceased performing with the band following its 2005 release FWX due to a reported aversion to touring. D'Virgilio played with the band on a handful of gigs supporting that album and appeared on the 2006 DVD release Live in Athens.
On July 26, 2011, D'Virgilio released a solo EP called Pieces. He performed a show in Quebec City, Canada performing the EP in its entirety with local musicians on the day of the album release.
On November 18, 2011, D'Virgilio announced that he had left Spock's Beard, because of his work with Cirque du Soleil: "It is very hard for me to write this, but as all good things come to an end at sometime or another, unfortunately I have to tell you all that my time with Spock's Beard has come to a close."
In early 2014, D'Virgilio appeared on Strattman's album The Lie of the Beholder stating: "Recording the drums for Roy's record was a total blast. I am really honored that he asked me to be a part of his new musical adventure. The record rocks and, from a drummer's perspective, I got to hit 'em hard and got challenged by the songs – 2 things drummers love. I really enjoyed the whole process and the music."