The objective of the present study was to retrospectively examine whether the addition of minoxidil to patients who were already treated with maximum doses of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers but who had not achieved target blood pressures, has any detrimental effect on proteinuria or renal function or whether its effect on blood pressure prove salutary. The clinical records of the patients seen at the Hypertension, Nephrology, Dialysis and Transplantation Clinic from June 1982 through May 2005 were reviewed to identify 54 patients (78% men, 82% African-American) who had taken minoxidil (with and without angiotensin inhibition and blockade) and who had documented 24-hour urines for creatinine clearance and quantification of proteinuria before the initiation of minoxidil and after the blood pressure had stabilized on its final dose. The study was done at the Hypertension, Nephrology, Dialysis and Transplantation Clinic, the regional referral center for renal problems in eastern Alabama, USA. Minoxidil, whether alone or in combination with maximum doses of ACEIs and ARBs, was very successful in reduction of mean arterial pressure, but there was a tendency towards an increase in proteinuria. When minoxidil was given alone, patients demonstrated a trend towards reduction of proteinuria associated with blood pressure reduction; however, when minoxidil was added after the maximal doses of ACEIs and ARBs had been reached there was a significant increase in proteinuria (p = 0.017) on paired comparison in the same patients whose proteinuria had already demonstrated a significant decrease (p = 0.02) on the ACEI and ARB alone despite further significant reduction of blood pressure with the minoxidil (p = 0.003). Renal function deterioration to end stage renal disease correlated with increase in proteinuria (p = 0.03). We conclude that minoxidil was very effective in lowering systemic blood pressure but when given to patients already on maximum doses of ACEI and ARBs, there was an increase in proteinuria which could be interpreted as a detrimental effect having in mind that the blood pressure was significantly lowered.