Background: We have evaluate the effect of slow continuous ultrafiltration (SCUF) on cardiac output (CO) and other hemodynamic parameters related to the overall performance of the cardiovascular system in patients with congestive heart failure (CHF). Minimally invasive hemodynamic monitoring was performed via the radial artery using a pressure recording analytical method (PRAM) during SCUF treatment. Patients and Methods: Using PRAM, hemodynamic changes were assessed in 15 CHF patients (New York Heart Association (NYHA) class III–IV) treated with fluid overload removal by ultrafiltration. We analyzed the clinical and hemodynamic data recorded from 6 h before to 36 h after SCUF treatment. Results: Fluid removal was associated with clinical improvements, reductions in weight (7.4%, p < 0.01), edema and dyspnea, increased response to diuretics, and reductions in NYHA class (3.5 ± 0.52 to 2.4 ± 0.63, p < 0.01) and plasma pro-B-type natriuretic peptide (BNP) levels (21,810 ± 13,016 to 8,581 ± 5,549 pg/ml, p < 0.05). Clinical improvement was associated with significant variations in stroke volume (+17%, p < 0.05), CO (+19%, p < 0.05), cardiac power output (+19%, p < 0.05), dP/dtmax (+49%, p < 0.01), cardiac cycle efficiency (CCE; +0.44 units, p < 0.01), systemic vascular resistances (SVR; –12%, p < 0.05) and dicrotic pressure (–10%, p < 0.05) with respect to their baseline values. No significant variations in heart rate, and systolic and mean blood pressure were observed. Pro-BNP levels were found to correlate positively with both SVR (r = 0.96, p = 0.002) and NYHA class (r = 0.96, p = 0.037) and negatively with dP/dtmax (r = –0.83, p = 0.039), CCE (r = –0.93, p = 0.011) and CO (r = –0.94, p = 0.014). Conclusions: In CHF patients, ultrafiltration improves not only CO, as previously reported, but also contractile cardiac efficiency and performance. The PRAM system, a minimally invasive method, was able to record hemodynamic changes during SCUF treatment.