OBJECTIVE To investigate the association between cigarette smoking and the progression of diabetic nephropathy. RESEARCH DESIGN AND METHODS A prospective, follow-up study over one year was conducted in a sequential sample of 34 smokers, 35 nonsmokers, and 24 ex-smokers with type I diabetes, hypertension, and diabetic nephropathy. Progression of renal disease was defined according to the stage of nephropathy as an increase in proteinuria or serum creatinine or a decrease in the glomerular filtration rate. RESULTS Progression of nephropathy was less common in nonsmokers (11%) than in smokers (53%) and patients who had quit smoking (33%), P > 0.001. In a stepwise logistic regression analysis, cigarette pack years, 24-h sodium excretion, and GHb were independent predictive factors for the progression of diabetic nephropathy. Because blood pressure (BP) was well controlled in these patients and most values were within a normotensive range, neither standing, sitting, nor supine BP values were associated with progression of nephropathy. CONCLUSIONS Cigarette smoking represents an important factor associated with progression of nephropathy in treated hypertensive type I diabetic patients.