A piano concerto by Respighi was performed at Bologna in 1902; a “notturno” for orchestra was played at a concert in the Metropolitan Opera House that year. His comic opera Re Enzo and the opera Semirama brought him recognition and an appointment in 1913 to the St. Cecilia Academy in Rome as professor of composition. He became director of the conservatory in 1924 but resigned in 1926.

Respighi was drawn to the sensual, decadent climate of the Rome depicted by the poet Gabriele D'Annunzio, and in his celebrated suites—Pini di Roma (Pines of Rome, 1923–24) and Fontane di Roma (Fountains of Rome, 1914–16) especially—he sought to convey the subtlety and colour of the poet's imagination. Other suites include Vetrate di chiesa (Church Windows, 1927); Gli ucelli (The Birds, 1927); Feste Romane (Roman Festivals, 1929); and Trittico Botticelliano (Botticelli Triptych, 1927, for chamber orchestra).

Respighi was also drawn to old Italian music, which he arranged in three sets of Antique Dances and Arias (transcribed for orchestra from lute pieces). One of his most popular scores was his arrangement of pieces by Rossini, La Boutique fantasque, produced by Diaghilev's Ballets Russes in London (1919). A later arrangement of Rossini piano pieces, Rossiniana (1925), also became a ballet.

As a composer of opera, Respighi had less success outside his own country. His best known works for the theatre were Belfagor, a comic opera produced at Milan in 1923, and La fiamma (Rome, 1934), which effectively transfers the gloomy Norwegian tragedy of H. Wiers Jenssen (known to English-speaking audiences in John Masefield's version as The Witch) to Byzantine Ravenna. In a different, more subdued vein are the “mystery,” Maria Egiziaca (1932), and his posthumous Lucrezia (completed by his wife, Elsa; 1937), the latter showing Respighi's interest in the dramatic recitative of Claudio Monteverdi, of whose Orfeo he made a free transcription for La Scala, Milan, in 1935.

Respighi's wife and pupil, Elsa Olivieri-Sangiacomo Respighi (1894–1996), was a singer and a composer of operas, choral and symphonic works, and songs.