Trusting relationships among patients, physicians, and the health care system is important in encouraging self-care behaviors in cardiovascular patients. This study aimed to assess the prevalence of health care system and physician distrust in this population, compare the 2 forms of distrust, and describe the demographic, socioeconomic, and psychosocial predictors of high distrust. A total of 1,232 hospitalized adults with acute coronary syndrome or heart failure were enrolled in a prospective, observational study assessing health care system distrust and physician distrust. High health care system distrust (35%) was observed across the population, with lower levels of interpersonal physician distrust (16%). In a multivariate analysis, poor social support and coping skills were strong predictors of both health care system (p=.026, p=.003) and physician distrust (p<.001, p=.006). Individuals with low or marginal health literacy had a higher likelihood of physician distrust (p<.001), but no relation was found between health literacy and health care system distrust. In conclusion, distrust is common among acutely ill cardiac patients. Those with low social support and low coping skills are more distrusting of physicians and the health care system.