He worked in various publishing houses in Buenos Aires and was in charge of the Serie Negra which published well-known authors of crime fiction including Dashiell Hammett, Raymond Chandler, David Goodis and Horace McCoy.

A fan of American literature, he was also influenced by F. Scott Fitzgerald and William Faulkner, as well as by European authors Franz Kafka and Robert Musil.

Piglia's fiction includes several collections of short stories as well as highly allusive crime novels, among them Respiración artificial (1980, trans.

In 2013 he was diagnosed with amyotrophic lateral sclerosis; he died of the disease on January 6, 2017, in Buenos Aires, Argentina.

On January 4, 2018, his memory was honored in New York City at "Modos infinitos de narrar: Homenaje a Ricardo Piglia," an event at which academics discussed the impact of his work on Latin American literature and intellectual history and his legacy as a literary critic and scholar.