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Elevated central venous pressure (CVP), low cardiac output, and mild hypoxia are common early and late after Fontan operations. However, the association of these characteristics with late mortality is unclear. We aimed to elucidate the hemodynamic determinants of mortality after Fontan operation.We evaluated early (group early; 0.5-5 years postoperatively, n = 387) and late (group late; ≥15 years postoperatively, n = 161) Fontan hemodynamics that included CVP (mm Hg), cardiac index (CI; L/min per m2), systemic ventricular end-diastolic volume index (mL/m2), ejection fraction (EF; %), and arterial blood oxygen saturation (%). We examined the effect of these variables on 5-year all-cause mortality.Mortality was higher in group late than in group early (17 vs 11, P < .0001). In both groups, higher CVP (hazard ratio [HR]1.46 and 1.38, respectively; P < .001-.0001) and lower arterial blood oxygen saturation (HR 1.12, P < .001 for both) were associated with increased mortality. Greater end-diastolic volume index (HR per 20: 1.73) and lower EF (HR per 10%: 3.38) were associated with increased mortality only in group early (P < .0001 for both). In contrast, only in group late was higher CI associated with increased mortality (HR 2.50, 95% CI 1.30-4.55, P < .01). Seven patients in group late with both high CVP (≥14) and CI (≥3.0) had the highest mortality (HR 18.1, 5.55-52.4, P < .0001).Elevated CVP and low arterial blood oxygen saturation correlate with mortality in both early and late Fontan survivors. End-diastolic volume index and EF are associated with mortality only in the earlier cohort, whereas interestingly, elevated cardiac output is associated with increased mortality in the later cohort.