BACKGROUND: This study evaluated the efficacy of ulinastatin for attenuating organ injury and the release of proinflammatory cytokines due to cardiopulmonary bypass (CPB) during cardiac surgery. METHODS: Patients undergoing valvular heart surgery employing CPB were assigned to receive either ulinastatin (group U, n = 13) or a placebo (group C, n = 11) before the commencement of CPB. Hemodynamic data, parameters of major organ injury and function, and proinflammatory cytokines were measured after the induction of anesthesia (T1), after CPB (T2), at the end of anesthesia (T3), and at 24 hours after surgery (POD). RESULTS: The demographic data, CPB duration, and perioperative transfusions were not different between the groups. PaO2/FiO2 in group U was significantly higher than that in group C at T3 (3.8 +/- 0.8 vs. 2.8 +/- 0.7, P = 0.005) and at POD (4.0 +/- 0.7 vs. 2.8 +/- 0.7, P < 0.001). Creatine kinase-MB at POD in group U was significantly lower than that in group C (17.7 +/- 8.3 vs. 33.7 +/- 22.1, P = 0.03), whereas troponin I at POD was not different between the groups. Creatinine clearance and the extubation time were not different between the groups at POD. The dopamine infusion rate during the post-CPB period in group U was significantly lower than that in group C (1.6 +/- 1.6 vs. 5.5 +/- 3.3 microg/kg/min, P = 0.003). The interleukin-6 and tumor necrosis factor-alpha concentrations at T1, T2, and T3 as well as the incidences of postoperative cardiac, pulmonary and kidney injuries were not different between the groups. CONCLUSIONS: Ulinastatin pretreatment resulted in an improved oxygenation profile and reduced inotropic support, probably by attenuating the degree of cardiopulmonary injury; however, it did not reduce the levels of proinflammatory cytokines.