Background: Acute normovolemic hemodilution (ANH) is a blood conservation strategy in cardiac surgery, predominantly used in coronary artery bypass graft (CABG) and/or valve procedures. Although higher complexity cardiac procedures may benefit from ANH, concerns for hemodynamic instability, and organ injury during hemodilution hinder its wider acceptance. Laboratory and physiological parameters during hemodilution in complex cardiac surgeries have not been described. Study design and methods: This observational cohort (2019–2021) study included 169 patients who underwent thoracic aortic repair, multiple valve procedure, concomitant CABG with the aforementioned procedure, and/or redo sternotomies. Patients who received allogeneic blood were excluded. Statistical comparisons were performed between ANH (N = 66) and non-ANH controls (N = 103). ANH consisted of removal of blood at the beginning of surgery and its return after cardiopulmonary bypass. Results: Intraoperatively, the ANH group received more albumin (p =.04) and vasopressor medications (p =.01), while urine output was no different between ANH and controls. Bilateral cerebral oximetry (rSO2) values were similar before and after hemodilution. During bypass, rSO2 were discretely lower in the ANH versus control group (right rSO2 p =.03, left rSO2 p =.05). No differences in lactic acid values were detected across the procedural continuum. Postoperatively, no differences in extubation times, intensive care unit length of stay, kidney injury, stroke, or infection were demonstrated. Discussion: This study suggests hemodilution to be a safe and comparable blood conservation technique, even without accounting for potential benefits of reduced allogenic blood administration. The study may contribute to better understanding and wider acceptance of ANH protocols in high-risk cardiac surgeries.