As in much of Europe, the prosperity of Alsace came to an end in the 14th century by a series of harsh winters, bad harvests, and the Black Death. These hardships were blamed on Jews, leading to the pogroms of 1336 and 1339. In 1349, Jews of Alsace were accused of poisoning the wells with plague, leading to the massacre of thousands of Jews during the Strasbourg pogrom. Jews were subsequently forbidden to settle in the town. An additional natural disaster was the Rhine rift earthquake of 1356, one of Europe's worst which made ruins of Basel. Prosperity returned to Alsace under Habsburg administration during the Renaissance.

About when did Alsace lose its prosperity?