Crew members visited Vatican City as tourists and extensively photographed the city to capture as much detail as possible, knowing they were unlikely to be allowed to film there, so that they could recreate the sets as faithfully as possible.
Although the novel upon which this film is based is set before the events of the novel "The Da Vinci Code", the film has been written as a sequel to The Da Vinci Code (2006).
During filming in Rome, the crew and equipment were blocking the passage of a bridal party on its way to the church for a wedding. Upon discovering this situation, Tom Hanks personally escorted the party through the filming area and rallied the crew to remove the obstacles in the way. After the bride was delivered to the church (on time), her grateful family invited Hanks and director Ron Howard to stay for the wedding ceremony. Unfortunately, Hanks' and Howard's busy filming schedule prevented them from accepting the offer.
Ewan McGregor suggested to Ron Howard that he could do the sequence where the Camerlengo tells the Cardinals about the Illuminati entirely without breaking it into several segments; he felt that he could pull it off, having known all of his lines. Howard agreed to his suggestion and proceeded to film it. The take was so good that no further takes were shot and this was the one used in the film.
Leonardo DiCaprio turned down the role of Camerlengo Patrick McKenna despite being offered the role personally by Tom Hanks.