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Traditionally believed to have been instigated by Queen Catherine de' Medici, the mother of King Charles IX, the massacre took place a few days after the wedding day (18 August) of the king's sister Margaret to the Protestant Henry III of Navarre (the future Henry IV of France).

Many of the most wealthy and prominent Huguenots had gathered in largely Catholic Paris to attend the wedding.

The massacre began in the night of 23–24 August 1572 (the eve of the feast of Bartholomew the Apostle), two days after the attempted assassination of Admiral Gaspard de Coligny, the military and political leader of the Huguenots. The king ordered the killing of a group of Huguenot leaders, including Coligny, and the slaughter spread throughout Paris. Lasting several weeks, the massacre expanded outward to other urban centres and the countryside. Modern estimates for the number of dead across France vary widely, from 10,000 to 70,000.

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The massacre also marked a turning point in the French Wars of Religion. The Huguenot political movement was crippled by the loss of many of its prominent aristocratic leaders, as well as many re-conversions by the rank and file. Those who remained were increasingly radicalized. Though by no means unique, it "was the worst of the century's religious massacres".[2] Throughout Europe, it "printed on Protestant minds the indelible conviction that Catholicism was a bloody and treacherous religion".[3]