Objectives: We systematically reviewed the literature to address the question of which of the three hemodynamic factors predicts prognosis best in heart failure patients when directly compared to each other: cardiac output, preload or afterload. Methods: Prognostic studies in heart failure (HF) were searched that included at least two of the three hemodynamic variables: (1) cardiac output or cardiac index (CI), (2) preload represented by pulmonary capillary wedge pressure (PCWP) and (3) afterload simplified to systolic blood pressure (SBP). Critical appraisal was done according to the QUIPS format for prognostic studies. The main endpoint was all-cause mortality, which could be combined with other endpoints. We report the number of studies in which CI, PCWP and SBP remained significant prognostic predictors in multivariate analysis. We also assessed whether hemodynamic predictors of prognosis varied in four different HF-populations. Results: Included were 18 studies containing a multivariate analysis. PCWP was an independent predictor of prognosis in 10 of 18 studies, SBP in 3 of 14 studies and CI in none of 18 studies. Results were not specific for any of the HF-populations. Conclusions: A higher PCWP and lower SBP are independent predictors of poor prognosis in HF. In spite of the frequently used concept behind HF, this review demonstrates that CI is not an independent predictor of prognosis in HF.