Background: In June 2013, the FDA issued a Black Box Warning on synthetic colloids resulting from data indicating an increased risk of mortality, renal injury, and excess bleeding incidence in septic patients admitted to the Intensive Care Unit (ICU), and patients undergoing coronary artery bypass graft (CABG) surgery. The purpose of this study was to compare the incidence of mortality, incidence/severity of renal injury and bleeding in septic ICU patients, and patients undergoing CABG surgery who have received hydroxyethyl starch 130/0.4 or albumin. Methods: This was a retrospective, single center, cohort study conducted at a 433 bed tertiary care hospital in Lexington, Kentucky. Computer generated lists provided patients who received hydroxyethyl starch 130/0.4 or albumin during inpatient stay as either a sepsis patient in the ICU or post coronary artery bypass graft patient. All cause mortality was the primary endpoint and secondary endpoints included overall renal dysfunction, incidence of bleeding, and overall length of stay. Results: A total of 89 patients were evaluated that received albumin or hydroxyethyl starch 130/0.4 alone with either septic ICU or CABG diagnosis codes. There was no significant difference in all cause mortality (p = 0.64). Overall renal dysfunction showed no statistically significance between the two groups (p = 0.66). There was no statistically significant difference between the albumin or HES 130/0.4 arms with respect to bleeding (TIMI Minimal p = 0.57, TIMI Minor p = 0.69, TIMI Major p = 0.35). Patient who received albumin had a statistically significant longer hospital overall length of stay (p = 0.003). Conclusion: There was no difference between HES 130/0.4 and albumin in mortality, renal dysfunction, and bleeding in septic ICU and CABG patients. Patients receiving albumin had an increased overall length of stay. These findings suggest that hydroxyethyl starch 130/0.4 may be safe in the studied patient populations; however, further investigation into specific HES agents should be conducted.