Objective To measure public trust in a health information sharing in a broadly defined health system (system trust), inclusive of health care, public health, and research; to identify individual characteristics that predict system trust; and to consider these findings in the context of national health initiatives (e.g., learning health systems and precision medicine) that will expand the scope of data sharing. Data Sources Survey data (n = 1,011) were collected in February 2014. Study Design We constructed a composite index of four dimensions of system trust—competency, fidelity, integrity, and trustworthiness. The index was used in linear regression evaluating demographic and psychosocial predictors of system trust. Data Collection Data were collected by GfK Custom using a nationally representative sample and analyzed in Stata 13.0. Principal Findings Our findings suggest the public's trust may not meet the needs of health systems as they enter an era of expanded data sharing. We found that a majority of the U.S. public does not trust the organizations that have health information and share it (i.e., the health system) in one or more dimensions. Together, demographic and psychosocial factors accounted for ~18 percent of the observed variability in system trust. Future research should consider additional predictors of system trust such as knowledge, attitudes, and beliefs to inform policies and practices for health data sharing.