Background: The presence of nephrotic-range proteinuria in a nondiabetic hypertensive patient is generally indicative of an underlying glomerular disease. A few published reports have noted nephrotic proteinuria in some patients with hypertensive nephrosclerosis. The frequency of this association is unknown. Methods: We retrospectively reviewed renal biopsy reports on all cases of nephrotic syndrome over an 8-year period (1993–2000). We excluded all cases of diabetes mellitus, lupus, hepatitis, human immunodeficiency virus, and chronic use of nonsteroidal anti-inflammatory drugs. Biopsy specimens showing glomerular eosinophilic hyalinosis lesions, positive immunofluorescence staining, or dense deposits on electron microscopy were also excluded. Thirteen of the remaining 237 (5.5%) biopsy specimens satisfied the standard histological criteria for hypertensive nephrosclerosis. Results: All patients were African-Americans with a mean age of 47.5 ± 13 years and an average mean arterial blood pressure of 122 ± 19 mm Hg. The mean values for urinary protein excretion, serum creatinine, albumin, and cholesterol were 8.9 g/day, 3.3 mg/dl, 3.1 g/dl, and 245 mg/dl, respectively. Optimal blood pressure control required at least three antihypertensive agents. Progression to end-stage renal disease occurred over a mean duration of 8.3 ± 6.5 months. Multivariate regression showed a strong but nonsignificant association between the level of proteinuria at the time of biopsy, duration of hypertension, and number of blood pressure medications (R 2 = 0.56, p = 0.38). Conclusions: Nephrotic syndrome may be more common in poorly controlled essential hypertension than previously realized. In African-American patients, the differential diagnosis of nephrotic syndrome should include hypertensive nephrosclerosis, but abrogation of renal biopsy is not implied.