Existing systematic reviews have insufficiently delineated the differing cardiac and renal profile of ultrafiltration compared to diuretics as a method of decongestion in acute decompensated heart failure. This meta-analysis will investigate the impact of ultrafiltration compared to diuretics on prognostic cardiac and renal biomarkers. We searched PubMed Central, Ovid MEDLINE®, Ovid Embase, all EBM reviews, and Web of Science Core Collection for randomised controlled trials published before 21 July 2022. Our main outcome measures were cardiac (brain natriuretic peptide and N-terminal pro-brain natriuretic peptide) and renal biomarkers (serum creatinine, serum sodium, and blood urea nitrogen). A total of 10 randomised trials were included in our analysis after screening. An inverse-variance random effects meta-analysis of the pooled results demonstrated no significant difference between ultrafiltration and diuretics for 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 mg/dL). Overall, ultrafiltration produces a similar impact on prognostic cardiac and renal biomarkers when compared to diuretic therapy. We highlight ultrafiltration’s significant impact on short-term BUN and recommend further research to investigate more optimal protocols of ultrafiltration administration.