Abstract Background The purpose of this study was to retrospectively analyze the impact of human albumin (HA) substitution on organ function in patients undergoing orthotopic liver transplantation (OLT). Methods We retrospectively analyzed chart data of 15 hypoalbuminemic patients who received continuous infusion of HA (100 g/d) for seven d following OLT and matched them with 15 control patients for severity scores at admission. Primary endpoint was a difference in mean “sequential organ failure assessment” (SOFA) score during 14 d following OLT. Secondary endpoints included SOFA subscores, length of intensive care unit (ICU) stay, ICU mortality, one‐yr mortality, fluid balance, colloid osmotic pressure (COP), serum albumin, and total protein concentrations. Results Substitution of HA was associated with a lower mean SOFA score as compared to control (11.0 ± 3.6 vs. 13.4 ± 3.7; p < 0.001). Patients treated with HA also exhibited lower cardiovascular SOFA subscore and higher COP, serum albumin, and total protein concentrations. There were no significant differences in fluid balance, length of ICU stay, ICU mortality, or one‐yr mortality. Conclusions The present data suggest that continuous infusion of HA may preserve cumulative organ function (as measured by SOFA score) with emphasis on cardiovascular function in patients following OLT.