Objective: There are still several concerns about the extensive and prolonged use of hydroxyethylstarch solution (HES) in critically ill patients. The effects of volume replacement with HES over 5 days on hemodynamics, laboratory data, and organ function were compared with volume therapy using human albumin (HA). Design: Prospective, randomized study. Setting: Clinical investigations on a surgical intensive care unit (ICU) of a university hospital. Patients: 150 traumatized patients (injury severity score > 15) and 150 postoperative patients with sepsis were analyzed. Interventions: Either 10 % low-molecular weight HES (HES-trauma, n = 75; HES-sepsis, n = 75) or 20 % HA (HA-trauma, n = 75; HA-sepsis, n = 75) was given for 5 days to maintain the pulmonary capillary wedge pressure (PCWP) between 12 and 15 torr. The entire management of therapy of the patients was performed by physicians who were not involved in the study and blinded to the infusion regimen. Measurements and results: In addition to extensive cardiorespiratory monitoring, several routine laboratory parameters for assessing pulmonary, renal, hepatic, and coagulation function were analyzed from arterial blood samples on the day of admission to the ICU and on the day of sepsis diagnosis, respectively (“baseline” value) and daily over the following 5 days. Mortality during and after the study did not differ significantly between the infusion groups. There were also no differences between the incidence of pulmonary, renal, or hepatic failure in the two subgroups. Mean arterial pressure, heart rate, and PCWP were similar in both subgroups, whereas cardiac index, oxygen delivery index, oxygen consumption index, and the ratio between the partial pressure of oxygen in arterial blood and fractional inspired oxygen were higher in the HES- than in the HA-treated groups. Standard coagulation parameters did not differ, albumin concentration increased significantly in both HA groups, and lactate concentrations decreased only in the HES-sepsis patients (from 2.8 ± 0.5 to 1.5 ± 0.4 mg/dl). Volume replacement using albumin was significantly (p Conclusions: Volume therapy with 10 % HES for 5 days in the ICU patient showed no disadvantages compared with an infusion regimen using 20 % albumin. Volume replacement using HES may even be associated with improved hemodynamics. HES appears to be a valuable and significantly cheaper alternative to albumin – even for prolonged volume therapy in the critically ill patient.