Intradialytic hypotension is a serious and frequent complication of hemodialysis; however, there is no evidence-based consensus definition of intradialytic hypotension. As a result, coherent evaluation of the effects of intradialytic hypotension is difficult. We analyzed data from 1409 patients in the HEMO Study and 10,392 patients from a single large dialysis organization to investigate the associations of commonly used intradialytic hypotension definitions and mortality. Intradialytic hypotension definitions were selected a priori on the basis of literature review. For each definition, patients were characterized as having intradialytic hypotension if they met the corresponding definition in at least 30% of baseline exposure period treatments or characterized as control otherwise. Overall and within subgroups of patients with predialysis systolic BP<120 or 120-159 mmHg, an absolute nadir systolic BP<90 mmHg was most potently associated with mortality. Within the subgroup of patients with predialysis BP≥160 mmHg, nadir BP<100 mmHg was most potently associated with mortality. Intradialytic hypotension definitions that considered symptoms, interventions, and decreases in BP during dialysis were not associated with outcome, and when added to nadir BP, symptom and intervention criteria did not accentuate associations with mortality. Our results suggest that nadir-based definitions best capture the association between intradialytic hypotension and mortality.