ABSTRACT: Background: NaCl 7.2%/6% hydroxyethyl starch (HES) 200/0.5 (HSH) has shown its beneficial effects in cardiac surgery and immunomodulatory values in experiment and human studies. However, there is concern regarding detrimental renal effects of chloride and HES in the intensive care setting. Objectives: The objective of this study was to evaluate the influence of HSH on kidney integrity and the level of inflammatory mediators in on-pump coronary artery bypass surgery patients. Design: This was a single-center, prospective, randomized, single-blind pilot study. Setting: This work was performed at a tertiary cardiothoracic referral center during the period from February to August 2012. Patients: Forty patients scheduled for on-pump coronary artery bypass surgery were included. Interventions: Patients were randomized to receive once either 7.2% NaCl/6% HES 200/0.5 (HSH group, n = 20) or placebo (0.9% NaCl; control group, n = 20) at a dose of 4 mL·kg−1 for 30 min after anesthesia induction. Main outcome measures: The primary end point was the incidence of acute kidney injury (AKI) defined according to the Kidney Disease: Improving Global Outcomes. Secondary end points were peak serum cystatin C, peak urine neutrophil gelatinase-associated lipocalin, plasma levels of interleukin 6 (IL-6), IL-10, intercellular adhesion molecule 1, and endothelial-leukocyte adhesion molecule (E-selectin). Results: The incidence of AKI within 48 h was similar between the groups (HSH: four patients [20%]; control: six patients [30%]). There was a significantly lower peak value for serum cystatin C in the HSH group (0.83 [0.73–0.89] mg·L−1) compared with the control group (1.02 [0.88–1.15] mg·L−1; P = 0.001). Patients in both groups had similar peak postoperative urine neutrophil gelatinase-associated lipocalin concentrations. NaCl 7.2%/6% hydroxyethyl starch 200/0.5 significantly reduces levels of IL-6 and IL-10 at 4 h after cardiopulmonary bypass and intercellular adhesion molecule 1 and E-selectin at 4 h after cardiopulmonary bypass and on postoperative day 1 (P < 0.05 for all). Conclusions: NaCl 7.2%/6% hydroxyethyl starch 200/0.5 does not lead to the increase in AKI incidence when used for the volume therapy in on-pump coronary artery bypass surgery patients. NaCl 7.2%/6% hydroxyethyl starch 200/0.5 usage enhanced neither tubular injury nor alteration of glomerular filtration. In addition, HSH can reduce the level of the inflammatory mediators after surgery.