Objectives. We estimated the number of deaths attributable to social factors in the United States. Methods. We conducted a MEDLINE search for all English-language articles published between 1980 and 2007 with estimates of the relation between social factors and adult all-cause mortality. We calculated summary relative risk estimates of mortality, and we obtained and used prevalence estimates for each social factor to calculate the population-attributable fraction for each factor. We then calculated the number of deaths attributable to each social factor in the United States in 2000. Results. Approximately 245000 deaths in the United States in 2000 were attributable to low education, 176000 to racial segregation, 162000 to low social support, 133000 to individual-level poverty, 119000 to income inequality, and 39000 to area-level poverty. Conclusions. The estimated number of deaths attributable to social factors in the United States is comparable to the number attributed to pathophysiological and behavioral causes. These findings argue for a broader public health conceptualization of the causes of mortality and an expansive policy approach that considers how social factors can be addressed to improve the health of populations. (Am J Public Health. Published online ahead of print June 16, 2011:e1-e10. doi:10.2105/AJPH.2010.300086).