The most deadly epidemic in Americas was the Smallpox epidemic of the 16th century, which was brought to the Americas by European colonists. It is estimated that this epidemic killed between 50 and 100 million people in the Americas, decimating the indigenous population. The disease spread rapidly through the population due to the lack of immunity among the native population and the lack of effective medical care. The Smallpox epidemic had a profound impact on the history and development of the Americas, as it weakened the indigenous population and made it easier for European colonists to establish control over the region.