In 1927, Louis Vierne nominated him as his assistant at Notre-Dame. Duruflé and Vierne remained lifelong friends, and Duruflé was at Vierne's side acting as assistant when Vierne died at the console of the Notre-Dame organ on 2 June 1937, even though Duruflé had become titular organist of St-Étienne-du-Mont in Paris in 1929, a position he held for the rest of his life. In 1930 he won a prize for his Prélude, adagio et choral varié sur le "Veni Creator", and in 1936 he won the Prix Blumenthal. In 1939, he premiered Francis Poulenc's Organ Concerto (the Concerto for Organ, Strings and Timpani in G minor); he had advised Poulenc on the registrations of the organ part. In 1943 he became Professor of Harmony at the Conservatoire de Paris, where he worked until 1970; among his pupils were Pierre Cochereau, Jean Guillou and Marie-Claire Alain.
In 1947 he completed probably the most famous of his few pieces: the Requiem op. 9, for soloists, choir, organ, and orchestra. He had begun composing the work in 1941, following a commission from the Vichy regime. Also in 1947, Marie-Madeleine Chevalier became his assistant at St-Étienne-du-Mont. They married on 15 September 1953. (Duruflé's first marriage to Lucette Bousquet, in 1932, ended in civil divorce in 1947 and was declared null by the Vatican on 23 June 1953.) The couple became a famous and popular organ duo, going on tour together several times throughout the sixties and early seventies.
He was made a Chevalier de la Legion d'honneur in 1954. He was promoted to an Officier de la Legion d'honneur in 1966.
Duruflé suffered severe injuries in a car accident on 29 May 1975, and as a result he gave up performing; indeed he was largely confined to his apartment, leaving the service at St-Étienne-du-Mont to his wife Marie-Madeleine (who was also injured in the accident). He died in Louveciennes (near Paris) in 1986, aged 84.
Duruflé was highly critical of his own compositions. He published only a handful of works and often continued to edit and change pieces after publication. For instance, the Toccata from Suite, op. 5 has a completely different ending in the first edition than in the more recent version, and the score to the Fugue sur le nom d'Alain originally indicated accelerando throughout. The result of this perfectionism is that his music, especially his organ music, tends to be well polished, and is still frequently performed in concerts by organists around the world.
Scherzo op. 2 (1926)
Prélude, adagio et choral varié sur le theme du 'Veni Creator' op. 4 (1926/1930)
For vocal soloists, choir and (large) orchestra (normally including organ, but can be performed without one): commissioned as a symphonic poem in 1941; completed in September 1947; first performed on 2 November 1947; published in 1950
For the same vocal forces and organ ("organ reduction" version; cello ad libitum in one movement): published in 1948
For the same vocal forces, organ and (reduced) orchestra (several instruments ad libitum, but one or more string instruments in every movement): published in 1961