Pacini's opera Saffo premiered at the Teatro San Carlo of Naples on November 29, 1840. The libretto was written by Salvatore Cammarano and is considered his finest poetic operatic text. This was the first collaboration between these two artists, but it nearly did not come to pass. Pacini began setting the text and then decided that the project was beyond his capabilities. He went to Cammarano and requested a different libretto. However, Cammarano demanded to hear Pacini's completed pieces first, so that he could make a judgment. When Pacini played him his initial efforts, the librettist is said to have thrown his arms around the composer and insisted that Pacini finish the score, for he was sure it would be a huge triumph for them both. Pacini's setting is extremely inspired and original, and the opera was indeed an outstanding success.

The composer turned to readings on Greek music and aesthetics for inspiration, and attempted to capture the atmosphere and character of the poet Saffo's world in his score. The opera is constructed out of just a few extremely extended musical numbers, which in turn are well integrated with one another into an almost continuous musico-drama. There are only three solo pieces, and all of these make some use of the chorus as well. Imaginative themes, creative rhythmic and compositional devices, stratospheric virtuosics, and an impassioned conclusion rival the greatest settings of Donizetti and demonstrate Verdi's indebtedness to Pacini's dramaturgy. The finale to the second act is breathtaking in its scope and dramatic tension, which build to a full, climactic stretta. Saffo's final moments are dramatically inspired; she goes completely mad and commits suicide. Beautiful lyricism, imaginative use of orchestral colors, formal innovation, and a keen understanding of Saffo's emotional turmoil propel the drama to its spectacular conclusion.

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