In 1957, Playboy magazine published a pictorial feature on Vargas' nudes, which drew the attention of publisher Hugh Hefner
When Vargas and Esquire went their separate ways in 1946, the artist immediately embarked upon a project to publish his own yearly calendar. In the meantime, the magazine published an Esquire Calendar for 1947 that consisted completely of unsigned Vargas paintings. By the time Vargas' 1948 calendar was published, Esquire had a court order barring the artist from selling or distributing any product bearing the name "Varga", which the magazine had copyrighted. In 1950, a court ruled that Vargas would have to sign all his subsequent paintings with his full name.
During the early and mid- 1950s, Vargas took on many commercial assignments, including a pin-up of Shelley Winters for the RKO film Behave Yourself, a deck of Vargas Girl playing cards called "Vargas Vanities", and a series of pinups for the pocket-sized British magazine Men Only. In 1957, Playboy magazine published a pictorial feature on Vargas' nudes, which drew the attention of publisher Hugh Hefner In August 1958, Vargas and Anna Mae travelled to Lima, Peru, for a highly successful exhibition of his paintings. They were greeted upon their return with a personal invitation from Hefner to have Vargas' work appear monthly in Playboy.
Embarking on this momentous association in 1960, Vargas was to paint 152 works for Playboy during this period, adapting to new moral standards and more explicit sexuality. Vargas painted only two front- cover images for Playboy during his long reign as the magazine's primary artist: a cut-out figure of a girl in a bathing suit that was part of a montage created by art director Reid Austin in 1961 and the cover for the March 1965 issue.
During the Esquire years, from 1940 to 1946, Vargas usually prepared a total of four preliminary studies for each published painting. Three of these were drawn on a fine tissue paper, the fourth on a heavy vellum parchment paper. The three tissues showed increasing detail from one state to the next until the parchment state which, because of the paper's colour and texture, was almost identical to the final painting. These studies would often be drawn with the model as a nude, Vargas simply adding the clothing to the final painting for publication. At Playboy, Vargas did one tissue and occasionally a few, parchment studies for each published painting.
When Vargas' wife passed away in November 1974, the artist lost much of his interest in painting and in life. Towards the end of the 1970s, he worked on an autobiography with Reid Austin, Vargas (Harmony Books). His career was revived somewhat when he painted an album cover, Candy-0, for The Cars; he also designed two other record album jackets for singer Bernadette Peters. He died on 30 December 1982, in Los Angeles.