Several common and functional genes are known to contribute to responsiveness to blood pressure (BP) therapy. BP therapy is typically guided by algorithms that do not include a patient’s genetic information. This study aimed to determine the impact of a multi-organ genetic panel on BP response to pharmacotherapy. Eighty-six patients completed one study visit consisting of a buccal swab collection, measurement of office BP, and a medical chart review for BP history. Genes analyzed included those that encode for one drug metabolizing enzyme, renal Na+ handling, vascular, and cardiac function. Relationships between genotype and control of BP (<140/<90), ∆ systolic BP, ∆ diastolic BP, and ∆ mean arterial BP were assessed. SLC12A3 resulted in a significant association between the target drug and the functional genotype for BP control (<140/<90 cut off) (p<0.05). Conversely, three of five renal genotypes were associated with BP control using 120/80 as a cut-off (p<0.05). Three of four cardiac genotypes were associated with the BP control at <140/<90, with one being statistically significant (position 49 of ADRB1). Only one vascular genotype was predictive of blood pressure control at <140/<90. We found a significant drop in mean BP from baseline in six genes, three important in the diuretic response and three in β-blockade (p<0.05 on target drug vs. not). These results demonstrate that a multi-gene panel for renal Na+ handling, vascular function, and cardiac output may influence the BP response to therapy, but larger studies with more statistical power are needed.