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From August 1370 Joanna travelled to Prague, where she was married on 29 September 1370 to Wenceslaus, son and heir of Emperor Charles IV by his third wife, Anna of Swidnica. The emperor had to obtain a papal dispense due to the close relatedness of the couple. The marriage was not consummated until 1376.
The conjugal bond suited the Luxembourg ruler to strengthen ties with the Bavarian duke, who held extensive estates in the Low Countries; nevertheless, Joanna was not the first choice of a bride for Wenceslaus. Charles IV had initially planned for him to marry the Hohenzollern princess Elisabeth of Nuremberg, but the marriage never took place, since Elisabeth married Rupert of the Palatinate instead.
The marriage lasted for sixteen years, however the couple had no children (it is said that Wenceslaus was infertile due to his alcoholism). Joanna died in 1386 at the age of thirty or thirty-one, allegedly from the consequences of an attack by Wenceslaus' hunting dogs.
Wenceslaus gave Johanna a magnificent funeral, which took place at Žebrák castle. According to custom, Joanna's body was exposed for a few days in Prague churches and was later buried in Prague Castle.
Wenceslaus later married Joanna's cousin, Sofia of Bavaria, but this marriage also bore no issue. Wenceslaus was deposed from the throne of Germany in 1400 and was succeeded by Elisabeth of Nuremberg's husband, Rupert.