Recent studies have concluded that the global pattern of neutral genetic diversity in humans reflects a series of founder effects and population movements associated with our recent expansion out of Africa. In contrast, regional studies tend to emphasize the significance of more complex patterns of colonization, gene flow, and secondary population movements in shaping patterns of diversity. Our objective in this study is to examine how founder effects, gene flow, and European admixture have molded patterns of neutral genetic diversity in the Americas. Our strategy is to test the fit of a serial founder effects process to the pattern of neutral autosomal genetic variation and to examine the contribution of gene flow and European admixture to departures from fit. The genetic data consist of 678 autosomal microsatellite loci assayed by Wang and colleagues in 530 individuals in 29 widely distributed Native American populations. We find that previous evidence for serial founder effects in the Americas may be driven in part by high levels of European admixture in northern North America, intermediate levels in Central America, and low levels in eastern South America. Geographically patterned admixture may also account for previously reported genetic differences between Andean and Amazonian groups. Though admixture has obscured the precise details of precontact evolutionary processes, we find that genetic diversity is still largely hierarchically structured and that gene flow between neighboring groups has had surprisingly little impact on macrogeographic patterns of genetic diversity in the Americas. Am J Phys Anthropol 2011. © 2011 Wiley Periodicals, Inc.