Background: Aortic stiffness as measured by pulse wave velocity (PWV) is a predictor of cardiovascular disease and other outcomes in different diseased and healthy populations, independent of traditional risk factors. The relationships between PWV measurement, global functional outcome and injury to the brain, kidney, and heart have never been examined in cardiac surgery patients. Objective: The objective of this project was to assess the relationship between aortic stiffness and health related quality of life (QoL), cognitive function, acute kidney injury (AKI), and cardiac function in patients undergoing aortic valve replacement (AVR). Methods: Aortic PWV, QoL, cognitive function, left ventricular (LV) function and NYHA class were assessed pre- and post-operatively (409 ± 159 days). The brain injury biomarker, N-methyl-D-aspartate receptor antibody (NR2Ab), was measured pre-operatively only. The biomarker of myocardial strain, B-type natriuretic peptide (BNP), and the novel AKI biomarker, neutrophil gelatinase-associated lipocalin (NGAL), were measured pre-operatively, and at 3 h and 18-24 h post-CPB. Results: Fifty-six patients (16 females; mean age, 71 ± 8.4 years) were included in this study, of which 50 (89%) patients attended the follow-up visit. No relationship was found between the degree of aortic stenosis (AS) and PWV, and AVR had no effect on aortic stiffness post-operatively. QoL and NYHA class significantly improved, while cognitive function did not deteriorate after AVR. High PWV is independently related to poorer QoL, cognitive function levels and NYHA class both pre- and post-operatively. PWV was not related to LV function, BNP or NGAL levels, but it was independently related to the level of NR2Ab. PWV did not correlate with AKI which was developed in 30% of the cases. Early post-operative plasma level of NGAL is the earliest predictive marker of post-operative AKI and the need for early medical renal intervention. Pre-operative BNP level was significantly and negatively correlated with pre-operative LV function, AS (valve area), and NYHA class in the post-operative follow-up period. Conclusion: In AVR patients, PWV is independently related to global functional status, cognitive function and brain injury biomarkers, but is not related to AKI or myocardial strain.