The team behind the global phenomenon The Da Vinci Code returns for the highly anticipated Angels & Demons, based upon the bestselling novel by Dan Brown. Tom Hanks reprises his role as Harvard religious expert Robert Langdon, who once again finds that forces with ancient roots are willing to stop at nothing, even murder, to advance their goals. Ron Howard again directs the film, which is produced by Brian Grazer, Ron Howard, and John Calley. The screenplay is by Akiva Goldsman and David Koepp. When Langdon discovers evidence of the resurgence of an ancient secret brotherhood known as the Illuminati - the most powerful underground organization in history - he also faces a deadly threat to the existence of the secret organization's most despised enemy: the Catholic Church. When Langdon learns that the clock is ticking on an unstoppable Illuminati time bomb, he jets to Rome, where he joins forces with Vittoria Vetra, a beautiful and enigmatic Italian scientist. Embarking on a nonstop, action-packed hunt through sealed crypts, dangerous catacombs, deserted cathedrals, and even to the heart of the most secretive vault on earth, Langdon and Vetra will follow a 400-year-old trail of ancient symbols that mark the Vatican's only hope for survival.

In 2003, Sony acquired the film rights to Angels & Demons along with The Da Vinci Code in a deal with author Dan Brown. In May 2006, following the film release of the film adaptation of The Da Vinci Code, Sony hired screenwriter Akiva Goldsman, who wrote the film adaptation of The Da Vinci Code, to adapt Angels and Demons. Producer Brian Grazer said they were too "reverential" when adapting The Da Vinci Code, which resulted in it being "a little long and stagey". This time, "Langdon doesn't stop and give a speech. When he speaks, he's in motion." David Koepp rewrote the script before shooting began. Filming was originally to begin in February 2008 for a December 2008 release, but because of the 2007-2008 Writers Guild of America strike, production was pushed back for a May 15, 2009 release. Shooting began on June 4, 2008 in Rome under the fake working title "Obelisk". The filmmakers scheduled three weeks of exterior location filming because of a predicted 2008 Screen Actors Guild strike on June 30. The rest of the film would be shot at Sony Pictures Studios in Los Angeles, California, to allow for this halt. Additionally, Roman Catholic Church officials found The Da Vinci Code offensive, so the the filmmakers were unable to shoot inside the churches Santa Maria del Popolo and Santa Maria della Vittoria. The Caserta Palace doubled for the inside of the Vatican, and the Biblioteca Angelica was used for the Vatican Library. A full scale replica was also built at Sony.

CBS News interviewed a priest working in Santa Susanna, who stated the Church did not also want their churches to be associated with scenes of murder. A tour guide also stated most priests do not object to tourists who visit out of interest after reading the book, a trend which will continue after people see the film. "I think they are aware that it's, you know, a work of fiction and that it's bringing people into their churches." Grazer deemed it odd that although The Da Vinci Code was a more controversial novel, they had more freedom shooting its film adaptation in London and France. Italian authorities hoped the filmmakers corrected the location errors in the novel, to limit the amount of explaining they will have to do for confused tourists.

The second unit took photographs of the Large Hadron Collider for visual effects shots of the facility. The Moving Picture Company would combine these into footage of actors shot against bluescreen in Los Angeles. Ron Howard also met with CERN to make the film more scientifically accurate. Filming also took place at the University of California, Los Angeles in July 2008.

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