Background: Prior studies of diastolic function in the setting of end-stage renal disease (ESRD) primarily utilize E/e’, a volume dependent measure of left ventricular (LV) filling pressure. While such studies show that high E/e’ is common and associated with adverse outcomes in ESRD, these findings may not be attributable to intrinsic diastolic function. In contrast to E/e’, the LV end-diastolic pressure-volume relationship (EDPVR) (a load independent index of LV diastolic compliance) describes intrinsic LV diastolic function. Therefore, we sought to examine the effects of hemodialysis on EDPVR, and to delineate correlates of EDPVR in the setting of ESRD. We hypothesized that E/e’ and other indices of diastolic function are volume dependent in ESRD, while EDPVR is not. Methods: Twenty-nine patients underwent echocardiography directly before and during the last hour of dialysis. LV diastolic compliance was quantified using a single-beat EDPVR method (P = αVβ). The LV end-diastolic volume at an idealized pressure of 20 mmHg (EDV20) was calculated as a means of comparing EDPVR curves within and between patients (smaller EDV20 = lower diastolic compliance). Results: During hemodialysis, EDV20 did not significantly change (median [IQR] pre-dialysis EDV20 112 [93-113] ml; intra-dialysis EDV20 113 [94-138] ml; p=0.2). However, E/e’ decreased on average by 1.2 absolute units (AU) (median [IQR] pre-dialysis 7.0 [6.0-8.9] AU; intra-dialysis 6.0 [5.1-9.7] AU; p=0.004). E/e’ decreased by 2 AU for every 1 L/hr ultrafiltration rate (p=0.07). Significant correlates of lower pre-dialysis EDV20 (stiffer LV) included higher diastolic blood pressure (DBP) (β=-13 ml EDV20 per 10 mmHg DBP, p=0.005) and concentric LV remodeling, (β=-5ml EDV20 per 0.1 g/ml LV mass/volume ratio, p=0.004). NT-proBNP was associated with higher E/e’, (β=0.2 E/e’ per 1000 pg/ml higher NT-proBNP, p<0.001), but was not a significant correlate of EDV20 (p=0.5). Conclusions: LV end-diastolic compliance (EDV20) is less volume dependent than LV filling pressures (E/e’) in the setting of ESRD, and thus may be a better measure of intrinsic diastolic function than E/e’. Further studies are needed to determine whether EDV20 predicts adverse outcomes in the ESRD population.