Naldi was selected by author Vicente Blasco Ibáñez for the role of Dona Sol in his film Blood and Sand. Naldi was signed with Famous Players-Lasky for the role. It was her first pairing with screen idol Rudolph Valentino and the film was a major success. It gave Naldi the image of a vamp which would follow her for the rest of her life. Naldi and Valentino were never romantic, and she would be one of the few to befriend his wife Natacha Rambova though that friendship would sour when the Valentinos divorced.
During this time, she posed for famous pin-up artist Alberto Vargas, who painted Naldi^[2] topless next to the bust of an imp.
While Valentino went on his one-man strike (preventing him from appearing in film) Naldi took on several Famous Players-Lasky roles with growing importance including The Ten Commandments (1923), directed by Cecil B. DeMille. When Valentino returned and fixed his contract woes she joined him for his final Famous Players-Lasky film, the now lost A Sainted Devil (1924). Naldi would leave the company as well soon after.