
In March 2018, he announced that he would once again leave BioWare to work on other things, including more original novels, co-creating a sci-fi graphic novel, and freelance gaming work. He later started working on Anthem in 2017. He returned to BioWare 3 years later in 2015 to focus on the post-release development of SWTOR. He left BioWare in February 2012 to focus more on his own projects.

Karpyshyn moved to Austin, Texas to help with Star Wars: The Old Republic. Mass Effect was named Game of the Year, in addition to receiving four other awards at the 2008 Elan Awards. His third book, Darth Bane: Path of Destruction was published by Del Rey Ballantine Books in 2006. His next major project was the Mass Effect series of games. He was later one of the lead writers and planners on Jade Empire, and worked on several games in the Baldur's Gate series. He wrote the scenario and much of the dialogue for Star Wars: Knights of the Old Republic, for which he would share the award for "Excellence in Writing" at the 2003 Game Developers Choice Awards. Karpyshyn joined the video game company BioWare in 2000.

He got his start as a game designer for Wizards of the Coast, and he also has written two novels for Wizards of the Coast, both published in 2001 and both set in the Forgotten Realms setting: Baldur's Gate II: Throne of Bhaal and Temple Hill. Following a car accident, he quit his job and returned to college, gaining a degree in English. Karpyshyn was at one point employed as a loan officer.
