Santana was a lifelong supporter of the Dominican revolt against the Haitian occupation and a noted general during the Dominican War of Independence (1844–1856). Unlike many of his political opponents who wanted to ultimately establish an independent Dominican state, Santana sought to reintegrate Hispaniola into the Spanish Empire. He oversaw the reestablishment of the Captaincy General of Santo Domingo as well as exile and imprisonment of a number of noted separatist and nationalist dissidents who had previously been his comrades during the war of independence. Under mounting pressure from the opposition which had been organizing a coup d'etat, he was forced to resign from his position. He died during the Dominican Restoration War, after which the country regained its independence.