The arrival of Europeans, namely the Spanish expeditions, to North America led to a dramatic reduction in the indigenous peoples population. Disease, war and other related in what amounted to a near extirpation of Native Americans. Disease was clearly the most influential factor in the depopulation of North America with smallpox the chief factor. More than 25 large-scale, multi-year smallpox outbreaks have been characterized and shown to influence the Native American populations from 1520 to 1797.
Smallpox war and other forces reduced the Native American population from some 5 million in pre-Columbian times to a low of a few hundred thousand in the 1800s. Although, historical estimations of pre-Columbian Native American Populations vary from 1 million to more than 100 million, 5 million is the population estimate from three different research report and is thus used in this work. As of the most recent census in Nov 2015, the Native American population has surpassed the estimated pre-Columbian population and now sits at 5.4 million.