Several films have adapted the book, among them:
- The Valley of Fear (1916), a silent film starring H.A. Saintsbury and Booth Conway
- The Triumph of Sherlock Holmes (1935), a British film starring Arthur Wontner as Holmes and Ian Fleming as Watson,
- Sherlock Holmes and the Deadly Necklace (1962), although intended to be an adaptation of The Valley of Fear, but only minor elements of the story remained in the final film.
- Sherlock Holmes and the Valley of Fear (1984), an animated film starring Peter O'Toole as the voice of Holmes
- The Valley of Fear, a recent and popular stage adaptation by Adrian Flynn for the Oxford Playscripts series, for amateur productions.
- The episode "The Case of the Pennsylvania Gun" of the 1954 Sherlock Holmes television series starring Ronald Howard as Holmes and Howard Marion Crawford as Watson.