It is not known whether serum potassium levels affect blood pressure response to antihypertensive medication. The African American Study of Kidney Disease and Hypertension (AASK) Genomics Study (N=828) is a subset of the AASK trial that randomized 1094 African American men and women with hypertensive nephrosclerosis to ramipril, amlodipine or metoprolol. Participants were also randomized to a usual (102-107 mm Hg) or low (≤92 mm Hg) mean arterial pressure (MAP) treatment goal. Time-to-event analyses were used to determine the relationship between serum potassium at randomization and time (days) to reach an MAP of 107 mm Hg. Mean baseline serum potassium was 4.22 mmol l(-1) (s.d.±0.56 and range 2.8-6.0) and the median days to reach target MAP was 32 (interquartile range 8-95). The adjusted hazard ratio (HR) for each 1 mmol l(-1) increase in serum potassium was 1.31 (95% confidence interval (CI): 1.08-1.59) in the usual MAP group, and 1.21 (95% CI: 1.02-1.44) in the low MAP group. Secondary findings suggested that women in the usual MAP group on amlodipine were more likely to reach target MAP compared with women randomized to ramipril (HR: 2.05, 95% CI: 1.30-3.21). Older subjects in the low MAP group (≥55 years) were also more likely to reach target MAP on amlodipine compared with ramipril (HR: 1.57, 95% CI: 1.03-2.38). Serum potassium appears to be a significant predictor of time to blood pressure response, independent of drug class. The effect of serum potassium on blood pressure response to antihypertensive medications needs to be further studied in different patient populations.