Identifying potential modifiable risk factors to reduce the incidence of vascular access thrombosis in hemodialysis could reduce considerable morbidity and health care costs. We analyzed data from a subset of 1426 HEMO study subjects to determine whether more frequent intradialytic hypotension and/or lower predialysis systolic BP were associated with higher rates of vascular access thrombosis. Our primary outcome measure was episodes of vascular access thrombosis occurring within a given 6-month period during HEMO study follow-up. There were 2005 total episodes of vascular access thrombosis during a median 3.1 years of follow-up. The relative rate of thrombosis of native arteriovenous fistulas for the highest quartile of intradialytic hypotension was approximately twice that of the lowest quartile, independent of predialysis systolic BP and other covariates. There was no significant association of intradialytic hypotension with prosthetic arteriovenous graft thrombosis after multivariable adjustment. Higher predialysis systolic BP was associated with a lower rate of fistula and graft thrombosis, independent of intradialytic hypotension and other covariates. In conclusion, more frequent episodes of intradialytic hypotension and lower predialysis systolic BP associate with increased rates of vascular access thrombosis. These results underscore the importance of including vascular access patency in future studies of BP management in hemodialysis.