In the late 1580s he was involved in a bitter polemic with Giason Denores, who objected in particular to Guarini's mixing of tragic and comic genres in his Pastor fido.

His most notable work, Il pastor fido, had its first dramatic representation in honor of the nuptials of the Duke of Savoy and Catalina Michaela of Austria in 1585[3] (published in 1590 in Venice; 20th rev.

This play, a pastoral tragicomedy about the loves and fates of shepherds and hunters, polished in style, was translated into many languages and became popular during the 17th century.

One of his poems, the erotic Tirsi morir volea, recounting the amorous encounter of a shepherd and a nymph, was set to music as a madrigal by more composers than any other pastoral poem of the era, including, among others, Andrea Gabrieli, Gioseppe Caimo, Carlo Gesualdo, Luca Marenzio, Benedetto Pallavicino, and Giaches de Wert.

[4] Another of Guarini's poems which was set by numerous madrigalists was Cor mio, deh non languire ("Dear heart, I prithee do not waste away").

While Guarini's work may be seen as lacking the deep feeling and sentiment of another poet at the Este court, Torquato Tasso, it was precisely this quality which commended it to musical setting at a time when excessive emotionalism had become unfashionable.