Abstract Background There are limited data comparing ultrafiltration with standard medical therapy as first-line treatment in patients with severe congestive heart failure (HF). We compared ultrafiltration and conventional therapy in patients hospitalized for HF and overt fluid overload. Methods and Results Fifty-six patients with congestive HF were randomized to receive standard medical therapy (control group; n = 29) or ultrafiltration (ultrafiltration group; n = 27). The primary end point of the study was rehospitalizations for congestive HF during a 1-year follow-up. Despite similar body weight reduction at hospital discharge in the 2 groups (7.5 ± 5.5 and 7.9 ± 9.0 kg, respectively; P  = .75), a lower incidence of rehospitalizations for HF was observed in the ultrafiltration-treated patients during the following year (hazard ratio 0.14, 95% confidence interval 0.04–0.48; P  = .002). Ultrafiltration-induced benefit was associated with a more stable renal function, unchanged furosemide dose, and lower B-type natriuretic peptide levels. At 1 year, 7 deaths (30%) occurred in the ultrafiltration group and 11 (44%) in the control group ( P  = .33). Conclusions In HF patients with severe fluid overload, first-line treatment with ultrafiltration is associated with a prolonged clinical stabilization and a greater freedom from rehospitalization for congestive HF.