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In 1991, Sean moved to Los Angeles, where he collaborated with math professor and former Angry Samoan Gregg Turner on Sante Fe, by The Mistaken for the independent label Triple X. This winsome CD garnered some pleasant press and appeared in the Top 35 radio airplay in Holland upon release. 1999 saw the release of 12 by The Mariettas, a powerful punk-pop quartet which included former members of several legendary LA-area groups; such as The Leaving Trains, Baby Lemonade and Arthur Lee and Love. 12 drew great notices in the US, as well as in the United Kingdom, in music magazines such as Luke and Bucketful of Brains.

Sean returned to his native Bay Area in 2001. He recorded several new songs acoustically and refined the material for Too Personal, the first solo CD of his career. Sean plays guitars throughout, though two guest musicians do appear on the album. Polly Klemmer, of The Mistaken, plays piano on two tracks. Also, on "The Answer is In", Sean is joined on acoustic guitar by his old friend Russ Tolman, solo recording artist and former guitarist of TRUE WEST. In 2006 Sean released Seed of Mayhem, featuring members of all of the above mentioned. That year he formed his permanent group, Sean O'Brien and His Dirty Hands: featuring Jeff Kane on lead guitar, Bill Davis on Bass, and Matt Shelley on drums. The Dirty Hands released their first CD, Goodbye Game, in 2008. The CD got a lot of great press. In 2009, The Drug of Memory was released. This compilation of tracks covers nearly thirty years of recorded work with the following bands: The Meantime, True West, Cottonmouth, The Mariettas and some solo work. The majority of these tracks have never been released. One track, "Smoke Me" features guest artist Chris Cacavas.