During the years 1908 and 1912 he composed his masterpiece «Անուշ» (Anoush), generally considered the "national opera of the Armenian people".

[4] Anoush, based on Hovhannes Tumanian's story of romance and tragedy, is a social drama distinguished by the originality of its national style, its folk characters, and its musical language.

[6] The next year, Tigranian moved once more back to Tiflis where he became an active member of the Armenian Music Society, he taught, and toured, performing his own compositions.

Following the establishment of the Soviet regime, Tigranian thoroughly reviewed and edited the opera Anoush in order to adhere to the principles of the new populist aesthetics.

The new edition was performed for the first time in Yerevan on 27 March 1935, and then in Moscow during the ten-day Festival of Armenian Arts on 22 October 1939.

The American premiere of Anoush took place on 27 May 1923 at the Lexington Avenue Opera House[7] in New York in a presentation marketed toward the Armenian immigrant audience.