BACKGROUND: In individuals with moderate to severe renal insufficiency, low protein intake may slow renal function decline. However, the long-term impact of protein intake on renal function in persons with normal renal function or mild renal insufficiency is unknown. OBJECTIVE: To determine whether protein intake influences the rate of renal function change in women over an 11-year period. DESIGN: Prospective cohort study. SETTING: Nurses' Health Study. PARTICIPANTS: 1624 women enrolled in the Nurses' Health Study who were 42 to 68 years of age in 1989 and gave blood samples in 1989 and 2000. Ninety-eight percent of women were white, and 1% were African American. MEASUREMENTS: Protein intake was measured in 1990 and 1994 by using a semi-quantitative food-frequency questionnaire. Creatinine concentration was used to estimate glomerular filtration rate (GFR) and creatinine clearance. RESULTS: In multivariate linear regression analyses, high protein intake was not significantly associated with change in estimated GFR in women with normal renal function (defined as an estimated GFR > or = 80 mL/min per 1.73 m2). Change in estimated GFR in this subgroup over the 11-year period was 0.25 mL/min per 1.73 m2 (95% CI, -0.78 to 1.28 mL/min per 1.73 m2) per 10-g increase in protein intake; the change in estimated GFR was 1.14 mL/min per 1.73 m2 (CI, -3.63 to 5.92 mL/min per 1.73 m2) after measurement-error adjustment for protein intake. In women with mild renal insufficiency (defined as an estimated GFR > 55 mL/min per 1.73 m2 but <80 mL/min per 1.73 m2), protein intake was significantly associated with a change in estimated GFR of -1.69 mL/min per 1.73 m2 (CI, -2.93 to -0.45 mL/min per 1.73 m2) per 10-g increase in protein intake. After measurement-error adjustment, the change in estimated GFR was -7.72 mL/min per 1.73 m2 (CI, -15.52 to 0.08 mL/min per 1.73 m2) per 10-g increase in protein intake, an association of borderline statistical significance. High intake of nondairy animal protein in women with mild renal insufficiency was associated with a significantly greater change in estimated GFR (-1.21 mL/min per 1.73 m2 [CI, -2.34 to -0.33 mL/min per 1.73 m2] per 10-g increase in nondairy animal protein intake). CONCLUSIONS: High protein intake was not associated with renal function decline in women with normal renal function. However, high total protein intake, particularly high intake of nondairy animal protein, may accelerate renal function decline in women with mild renal insufficiency.