Abstract African Americans (AAs) have a high prevalence of hypertension and suffer a disproportionately high risk for cardiovascular disease compared to whites. Apparent treatment-resistant hypertension (aTRH) is a severe form of hypertension defined as requiring ≥ 4 antihypertensive medications to achieve blood pressure (BP) control. An estimated 9 million US adults have aTRH. Given the rigorous clinical work-up needed to rule out pseudoresistance and therefore, diagnose true TRH, the population prevalence of TRH is not known. We propose an ancillary study to the Jackson Heart Study (JHS), a large prospective cohort of AA adults (n=5,306) that will deeply phenotype participants with aTRH, ruling out pseudoresistance (i.e., inaccurate clinic BP measurement, presence of a white coat effect, suboptimal antihypertensive therapy, and poor medication adherence) and secondary causes of hypertension (i.e., primary aldosteronism, obstructive sleep apnea, and kidney disease). The JHS provides a highly feasible setting for the proposed study as it includes a large population of AAs with a high prevalence of hypertension and extensive data collection as part of an upcoming fourth parent study visit, which will facilitate the screening and recruitment of participants for our ancillary study. Based on data collected during the fourth JHS exam, we will identify 400 participants with aTRH and 200 treatment-responsive controls. These participants will undergo a clinical evaluation for TRH including assessment of existing ambulatory BP monitoring (ABPM) data to detect white coat effect and urinalysis of antihypertensive drugs and metabolites to assess medication adherence. Also, participants with aTRH will be compared to treatment responsive controls with respect to secondary causes of hypertension and lifestyle factors. Clinical translation of the study findings will be facilitated by an external panel of experts who co-authored the American Heart Association 2018 Scientific Statement on Resistant Hypertension. Overall, the diagnosis and treatment of TRH is limited by our understanding of pseudoresistance and other factors underlying aTRH. The proposed study is urgently needed to more efficiently diagnose and better treat this severe form of hypertension among African Americans.