The Makropulos Affair (Czech Věc Makropulos) is a play written in 1922 by Karel Čapek that was turned into an opera by the Czech composer Leoš Janáček. Janáček's penultimate opera, it was, like so much of his work, inspired by his infatuation with Kamila Stösslová, a married woman much younger than himself.

Janáček's operatic version was written between 1923 and 1925. He had seen the play early into its run in Prague on December 12, 1922, and immediately saw its potential. He entered into a correspondence with Čapek, who was accommodating towards the idea, although legal problems in securing the rights to the play delayed work. When these problems were cleared on September 10, 1923, Janáček began work on the opera straight away. He wrote the libretto himself, and by December 1924 had completed the first draft of the work. He spent another year refining the score, before completing it on December 3, 1925.

Janáček had a penchant for choosing unusual stories for his operas, and The Makropulos Affair is a notable example. The heroine of this work, Emilia Marty, is a woman who has managed to live more than 300 years through the use of a miraculous elixir created by her father in the sixteenth century. When circumstances force her to reveal this secret, she succumbs to the realization that she has longed for death, and renounces the potion for herself.

The world premiere of the opera was given at the National Theatre in Brno on December 18, 1926, conducted by František Neumann . It was given in Prague two years later, and in Germany in 1929, but did not become really popular until a production by the Sadler's Wells company in London in 1964.