Having fallen somewhat out of favor with the Castro regime (the government's ban on a documentary on Havana nightlife made by his brother led to his being forbidden to publish in Cuba), he served from 1962 to 1965 in Brussels, Belgium, as a cultural attaché.

In 1966 he published Tres tristes tigres, a highly experimental, Joycean novel, playful and rich in literary allusions, which intended to do for Cuban Spanish what Mark Twain had done for American English, recording the great variety of its colloquial variations.

[5] Although he is considered a part of the famed Latin American Boom generation of writers that includes his contemporary Gabriel García Márquez, he disdained the label.

Ever an iconoclast, he even rejected the label "novel" to describe his most acclaimed works, such as Tres tristes tigres and La Habana para un infante difunto.

Cabrera Infante also translated James Joyce's Dubliners into Spanish (1972) and wrote screenplays, including Vanishing Point and the adaptation of Malcolm Lowry's Under the Volcano.