La Isabela, the first permanent European colony in America after the first failure of the colony of La Navidad (the present-day beach of the Saint-Nicolas mole in Haiti), was founded on 10 December 1493 by Christopher Columbus and named La Isabela in honour of Isabella the Catholic. The city, which was to become the capital, was soon abandoned because of poor drinking water resources, epidemics and difficulties in anchoring ships. In 1496, the city of Nueva lsabela was founded on the south coast of the island of Quisqueya. The latter was ravaged by a cyclone in 1502 and quickly rebuilt on the other bank of the river (Santo Domingo).

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