The book's first edition contained numerous inaccuracies of location of places in Rome, as well as incorrect uses of Italian language. Some of the language issues were corrected in the following editions.
Aside from the explicit introduction, the book depicts various fictional experts explaining matters in science, technology, and history in which critics have pointed out inaccuracies. An example of this is the antimatter discussions, wherein the book suggests that antimatter can be produced in useful and practical quantities and will be a limitless source of power. CERN published an FAQ page about Angels & Demons on their website stating that antimatter cannot be used as an energy source because creating it takes more energy than it produces.
Angels & Demons Decoded, a documentary on the American cable television network, The History Channel, premiered on May 10, 2009, shortly before the release of the novel's film adaptation. The documentary explores the various bases of the novel's story, as well as its inaccuracies. A CERN official, for example, points out that over the last 20 years, approximately 10 billionths of a gram of antimatter has been produced at the facility, whose explosive yield is equivalent to that of a firecracker, far less than is needed for it to be the threat depicted in the novel.
According to The Boston Globe language columnist Ben Zimmer, the Devil's Advocate, which is indicated in the novel to have a role in the selection of the pope, has nothing to do with the papal conclave, and was instead employed to present arguments against the proposed canonization of a person as a saint. Zimmer adds that the Devil's Advocate was abolished by Pope John Paul II in 1983, 17 years before the novel was published.