The long-term prognostic associations of pre- and post-dialysis blood pressures, interdialytic weight gain, and antihypertensive use in hemodialysis patients are unclear. The United States Renal Data System (USRDS) Dialysis Morbidity and Mortality Waves 3 and 4 Study, a randomly generated sample of 11,142 subjects receiving hemodialysis on December 31, 1993, was examined, with vital status followed until May 2000. Pre- and post-dialysis blood pressure values, interdialytic weight gain and number of antihypertensives averaged 151.8/79.7, 137.0/74, 3.6% and 0.76, respectively. Prognostic discrimination was maximized by considering pre- and post-systolic and diastolic blood pressure values simultaneously, in a pattern suggesting that wide pulse pressures were associated with mortality (P < 0.0001). Comorbidity adjustment markedly affected associations, with low pre-dialysis diastolic (P < 0.05), low post-dialysis dialysis diastolic pressure (P < 0.05), high post-dialysis dialysis systolic pressure (P < 0.05), and high interdialytic weight gains (P = 0.005) associated with mortality. Each class of antihypertensive drug, except angiotensin-converting enzyme (ACE)-inhibitors, was associated with lower mortality in unadjusted models, an effect most pronounced for beta-blockers (hazards ratio 0.72, 95% CI 0.66 to 0.79, P < 0.0001). Comorbidity adjustment eliminated survival associations for each antihypertensive class except beta-blockers. Pre- and post-dialysis blood pressure values have independent associations with mortality, in a way that implicates wide pulse pressures. Much of the adverse prognosis of wide pulse pressures probably reflects older age and cardiovascular comorbidity. Large interdialytic weight gains are associated with shorter survival when comorbidity is taken into account. Beta-blocker use shows a robust association with survival, and may be protective.