Introduction: Acute decompensated heart failure (ADHF) is a leading cause for hospitalizations in the US. Intravenous loop diuretics are the first-line therapy for ADHF but 40% of patients are discharged with unresolved congestion resulting in higher re-hospitalization and mortality rates. Ultrafiltration (UF) is a promising intervention that allows rapid removal of isotonic fluid in patients with ADHF. Studies comparing UF to diuretics have been inconsistent in their results regarding clinical outcomes. In this meta-analysis we aim to demonstrate that UF is associated with improvements in decongestion, clinical symptoms and mortality compared to diuretic use. Methods: A comprehensive literature search was performed to identify all RCTs from PubMed, EMBASE and Cochrane. Trials were included if they met following criteria: (1) randomization with a control group (2) comparison of UF with a loop diuretic and (3) a diagnosis of ADHF. The pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated by using a fixed-effects model if no heterogeneity was detected among the studies. A random effects model was applied if significant heterogeneity remained using the fixed effects analysis. A p-value of 0.05 was used to denote statistical significance. Results: Nine RCTs, including 605 patients (303 received diuretics, 302 received UF), were included in meta-analysis. When compared to diuretics, UF was associated with a reduced risk of clinical worsening (OR 0.57, 95% CI: 0.38-0.86, p-value 0.007), an increased likelihood for clinical decongestion (OR 2.32, 95% CI: 1.09-4.91, p-value 0.03), greater weight reduction (0.97 Kg, 95% CI: 0.52 - 1.42, p-value <0.0001) and greater volume reduction (1.11 L, 95% CI: 0.68-1.54, p-value <0.0001). The overall risk of re-hospitalization (OR 0.92, 95% CI: 0.62-1.38, p-value 0.70) and risk of return to emergency department (OR 0.69, 95% CI: 0.44-1.08, p-value 0.10) were not significantly improved by UF treatment. UF was not associated with a reduced risk of mortality (OR 0.99, 95% CI: 0.60-1.62, p-value 0.97). Conclusions: UF is associated with significant improvements in clinical decongestion and volume reduction but not in rates of re-hospitalization, return to emergency department or mortality.