Introduction: Female patients are at elevated risk for adverse mental health outcomes following hospital admission for ischemic heart disease. These psychosocial characteristics are correlated with unacceptably higher rates of cardiovascular (CV) morbidity and mortality. Guidelines to address mental health following acute coronary syndrome (ACS) can only be developed with the aid of studies elucidating which subgroups of female patients are at the highest risk. Methods/Design: The Female Risk factors for post-Infarction Depression and Anxiety (FRIDA) Study is a prospective multicenter questionnaire-based study of female participants admitted to hospital with ACS. Data are collected within 72 h of admission as well as at 3 and 6 months. At baseline, participants complete a sociodemographic questionnaire, social support survey, and Hospital Depression and Anxiety Scale (HADS). Follow-up will consist of a demographic questionnaire, HADS, changes to health status, and quality of life indicators. Statistical analysis will include descriptive and inferential methods to observe baseline distributions and significance between groups. Discussion/Conclusion: Our primary outcome is to determine if specific CV and sociodemographic factors correlate with increased depression and anxiety scores (HADS-D >7; HADS-A >7) at baseline. Our secondary aim is to determine if increased HADS scores at baseline and follow-up correlate with 3 and 6-month health and quality of life outcomes. A total of 2,000 patients will be enrolled across seven study sites. The aim of the FRIDA Study is to understand which groups of female patients have the highest rates of depression and anxiety following ACS to better inform care.