An elevated serum phosphate level in hemodialysis patients has been associated with mineral deposition in blood vessels. We studied a possible physiologic consequence of hyperphosphatemia by examining the relation between serum phosphate levels and blood pressure in 707 incident hemodialysis patients from 75 clinics who were enrolled in a prospective cohort study. We conducted cross-sectional and longitudinal multiple linear regression analyses, adjusting for demographics, medical history, and laboratory factors. In cross-sectional analyses at baseline, elevated serum phosphate was associated with higher predialysis systolic blood pressure (SBP) and pulse pressure (PP) at the start of dialysis; each 1 mg/dL higher phosphate level was associated with 1.77 mm Hg higher SBP. In multivariable adjusted longitudinal analyses, for each 1 mg/dL higher serum phosphate at baseline, SBP was higher at 3 months, 1.36 mm Hg (P = .005); 6 months, 1.13 mm Hg (P = .035); 12 months, 1.65 mm Hg (P = .008); 18 months, 1.44 mm Hg (P = .031); and 27 months, 2.54 mm Hg (P = .002). PP was higher at 3 months, 0.80 mm Hg (P = .027); 6 months, 0.91 mm Hg (P = .022); 12 months, 1.45 mm Hg (P < .001); 18 months, 1.06 mm Hg (P = .026); and 27 months, 1.37 mm Hg (P = .020). This study suggests that serum phosphate level is strongly and independently associated with blood pressure in hemodialysis patients. The effect of rigorous control of serum phosphate levels on arterial stiffness and blood pressure should be studied in clinical trials.