Prostacyclin (PGI(2)) analogous are potent antithrombotics recommended as prefilter infusion during renal replacement therapy (RRT) when heparin is contraindicated. It is debated whether PGI(2) administration during RRT affects transfusion requirements and outcome. Retrospective cohort study of all patients at a general intensive care unit (ICU) receiving continuous RRT (CRRT) in a 14-month period. Patients were stratified according to the used anticoagulant, that is prefilter PGI(2) group (n=24) and prefilter heparin group (n=70). The ICU stay of the patients was divided into three time periods: before, during and after CRRT. For each time period, laboratory values were analysed as changes/day and blood transfusion requirements as absolute values. Organ failures during the ICU stay and 1 year all-cause mortality were registered. During CRRT the PGI(2) group had a higher incidence of disseminated intravascular coagulation (DIC) (P=0.006), severe thrombocytopenia (P=0.03), higher maximum Sequential Organ Failure Assessment score (P<0.001) and higher rate of blood transfusions (P=0.006) compared to the heparin group. However, patients in the PGI(2) group tended to have lower mortality rates compared to those in the heparin group (30 days, 21 vs. 39%, P=0.12; 90 days, 34 vs. 53%, P=0.10 and 365 days, 38 vs. 57%, P=0.09). Patients receiving prefilter PGI(2) during CRRT were more severely ill and required more blood transfusions. Despite this, a trend towards lower mortality was observed in the PGI(2) group suggesting beneficial effects of PGI(2) administration in ICU patients undergoing CRRT.