In recent years, there has been growing awareness of the significant burden of Chagas disease in the United States (US). However, epidemiological data on both prevalence and access to care for this disease are limited. The objective of this study is to provide an updated national estimate of Chagas disease prevalence, the first state-level estimates of cases of T. cruzi infection in the US and to analyze these estimates in the context of data on confirmed cases of infection in the US blood supply. In this study, we calculated estimates of the state and national prevalence of Chagas disease. The number of residents originally from Chagas disease endemic countries were computed using data on Foreign-Born Hispanic populations from the American Community Survey, along with recent prevalence estimates for Chagas disease in Latin America from the World Health Organization that were published in 2006 and updated in 2015. We then describe the distribution of estimated cases in each state in relation to the number of infections identified in the donated blood supply per data from the AABB (formerly American Association of Blood Banks). The results of this analysis offer an updated national estimate of 238,091 cases of T. cruzi infection in the United States as of 2012, using the same method as was used by Bern and Montgomery to estimate cases in 2005. This estimate indicates that there are 62,070 cases less than the most recent prior estimate, though it does not include undocumented immigrants who may account for as many as 109,000 additional cases. The state level results show that four states (California, Texas, Florida and New York) have over 10,000 cases and an additional seven states have over 5,000 cases. Moreover, since 2007, the AABB has reported 1,908 confirmed cases of T. cruzi infection identified through screening of blood donations. This study demonstrates a substantial burden of Chagas disease in the US, with state variation that reflects the distribution of at risk Latin American immigrant populations. The study lends important new insight into the distribution of this disease in the US and highlights the need for further research quantifying prevalence and incidence to guide interventions for control of Chagas disease across the US. Chagas disease is a parasitic infection that primarily affects poor populations in Latin America. However, awareness of this disease in the United States has increased in recent years. In this study, we utilize data from the American Community Survey and the World Health Organization to estimate the number of cases of Chagas disease in the United States. We find that there are an estimated 238,000 cases across the United States, along with four states that each has over 10,000 cases (California, Texas, New York and Florida). We also analyze data from the United States blood donation which shows that about 1,900 cases have been identified through blood donation. We conclude that there is still a substantial burden of Chagas disease in the US, though the burden is focused in certain geographic regions. We also highlight the need for further research to better quantify prevalence and incidence in order to guide interventions to diagnose and treat patients with Chagas disease across the US.