We studied the long-term efficacy and safety of medium-molecular-weight hydroxyethyl starch (HES) administered in doses above 20 mlkg−1 during major blood replacement therapy. Blood replacement for 50 patients used 6% HES 200/0.5 (HES group) or 5% albumin (ALB group) and additional blood components according to a defined protocol. We compared safety, efficacy and costs in 4 peri-operative days. Colloid administration on the day of surgery was 38.4 mlkg−1 (HES group) and 35.1 mlkg−1 (ALB group). Haemodynamic, coagulation and renal function parameters were similar. Although total serum protein was still different on the third postoperative day (53.45 gl−1 (HES group) and 60.6 gl−1 (ALB group) (p < 0.01)) the colloid osmotic pressure always remained above 19.5 (2.5) mmHg (HES group). Blood loss (3810 (1632) ml (HES group) and 3455 (1733) ml (ALB group)) and the requirement for blood components was comparable. Costs were reduced by 35% (p < 0.05) in the HES group. We conclude that using 6% HES 200/0.5 as the only colloid for treatment even of large blood loss is a safe and economic alternative to albumin.