Ultrafiltration (UF) has emerged as an alternative therapy for acute decompensated heart failure (ADHF) due to its physiological benefits such as improvement in neurohormonal activation. We performed a systematic review and a meta-analysis to evaluate the efficacy, safety, and the impact on outcomes for UF therapy as compared to conventional medical treatment. The PubMed and Cochrane databases were searched from inception to December 2015 for randomized controlled trials that examined UF therapy in ADHF and used diuretic-based regimens as the control group. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, we explored the impact on weight change, fluid removal, renal function, rehospitalization rate, and mortality. Mantel–Haenszel odds ratio (OR) was calculated for dichotomous data and weighted mean difference (WMD) for continuous data. Seven studies with a total of 771 patients met our selection criteria. UF therapy led to greater weight loss (WMD 1.35, 95 % CI 0.49–2.21, p < 0.01) and fluid removal (WMD 1.81, 95 % CI 1.01–2.62, p = <0.01) while the impact of UF on renal function was comparable with medical treatment (WMD 0.06, 95 % CI −0.11 to 0.22, p = 0.48), UF decreased heart failure rehospitalization rate (OR 0.60, 95 % CI 0.37–0.98, p = 0.04) but did not change mortality (OR 1.03, 95 % CI 0.68–1.57, p = 0.89). Compared with diuretic-based medical treatment, UF therapy is more efficient in decongestion of patients with ADHF. It does not have a deleterious impact on renal function and can improve heart failure-related rehospitalization rate, albeit without conferring a survival benefit.