Background: Hypertension is common in hemodialysis patients; however, the relationship between interdialytic weight gain (IDWG) and blood pressure (BP) is incompletely characterized. This study seeks to define the relationship between IDWG and BP in prevalent hemodialysis subjects.Study Design, Setting, & Participants: This study used data from 32,295 dialysis sessions in 442 subjects followed up for 6 months in the Crit-Line Intradialytic Monitoring Benefit (CLIMB) Study.Outcomes & Measurements: Mixed linear regression was used to analyze the relationship between percentage of IDWG (IDWG [%] = [current predialysis weight - previous postdialysis weight]/dry weight * 100) as the independent variable and systolic BP (SBP) and predialysis - postdialysis SBP (Delta SBP) as dependent variables.Results: In unadjusted analyses, every 1 % increase in percentage of IDWG was associated with a 1.00 mm Hg (95% confidence interval [CI], +/- 0.24) increase in predialysis SBP (P < 0.0001), 0.65 mm Hg (95% Cl, +/- 0.24) decrease in postdialysis SBP (P < 0.0001), and 1.66 mm Hg (95% Cl, +/- 0.25) increase in Delta SBP (P < 0.0001). After controlling for other significant predictors of SBP, every 1% increase in percentage of IDWG was associated with a 1.00 mm Hg (95% Cl, +/- 0.24) increase in predialysis SBP (P < 0.0001) and a 1.08 mm Hg (95% Cl, +/- 0.22) increase in Delta SBP with hemodialysis (P < 0.0001). However, in subjects with diabetes as the cause of end-stage renal disease, subjects with lower creatinine levels, and older subjects, the magnitude of the association between percentage of IDWG and predialysis SBP was less pronounced. The magnitude of percentage of IDWG on Delta SBP was less pronounced in younger subjects and subjects with lower dry weights. Results were similar with diastolic BP.Limitations: Hemodialysis BID measurements are imprecise estimates of BP and true hemodynamic burden in dialysis subjects.Conclusions: In prevalent hemodialysis subjects, increasing percentage of MING is associated with increases in predialysis BP and BP changes with hemodialysis; however, the magnitude of the relationship is modest and modified by other clinical factors. Thus, although overall volume status may impact on BP to a greater extent, day-to-day variations in weight gain have a modest role in BP increases in prevalent subjects with end-stage renal disease.