Aims Existing systematic reviews have not delineated, in sufficient detail, the differing renal and cardiac profile of ultrafiltration as compared to diuretic therapy as methods of decongestion in acute decompensated heart failure. This systematic review and meta-analysis aims to determine the impact of ultrafiltration as compared to diuretic therapy on prognostic cardiorenal biomarkers. Methods and results A literature search was performed through PubMed Central, Ovid MEDLINE ®, Ovid Embase, All EBM reviews and Web of Science Core Collection strategy for randomised controlled trials published before July 2022. All studies meeting the inclusion criteria were included. 10 randomised trials were included in our analysis after the final screening process. The main outcome measures of our study were cardiac (brain natriuretic peptide and N-terminal pro-brain natriuretic peptide) and renal biomarkers (serum creatinine, serum sodium and blood urea nitrogen). Following this, data was extracted for the outcomes of interest, patient characteristics and study protocols. An inverse variance random effects meta-analysis of the pooled results demonstrated no significant difference between ultrafiltration and diuretic therapy with regards to the following outcomes: brain natriuretic peptide, N-terminal pro-brain natriuretic peptide, creatinine, sodium and long-term blood urea nitrogen. However, ultrafiltration produced statistically greater increases in blood urea nitrogen in the short-term (mean difference, 3.88; 95% confidence interval 0.59-7.17). Conclusion Our meta-analysis indicates that ultrafiltration produces a non-inferior impact on cardiorenal biomarkers when compared to diuretic therapy. We highlight clinically relevant caveats to this conclusion and recommend further research to determine more optimal protocols of administration.