Experimental evidence has demonstrated that hyperbaric oxygen (HBO) preconditioning prior to ischemic reperfusion injury (IRI), limits myocardial infarct size(1). This cardioprotective mechanism involves the expression of myocardial endothelial nitric oxide synthase (eNOS) and heat shock protein 90 (Hsp90)(2). IRI also occurs in patients during coronary artery bypass graft surgery (CABG). This study clinically assessed the effects of HBO preconditioning prior to IRI on the myocardial eNOS and Hsp72 expression and, myocardial function following IRI. This randomised control study of patients experiencing IRI during CABG involving cardiopulmonary bypass (CPB), consisted of 40 and 41 patients in Groups A (Control Group) and B (HBO Group), respectively. HBO preconditioning started 4 hours prior to CABG for 90 minutes at 2.4 ATA using 100% oxygen. Right atrial biopsies were sampled post anaesthetic induction, 5 minutes following the onset of CPB, 5 post ischemic reperfusion and 5 minutes post CPB. Atrial protein extracts were analysed for eNOS and Hsp72 via a quantitative sandwich ELISA. Pulmonary artery catheters measured heamodynamic parameters post induction, 5 minutes, 2, 4, 8, 12 and 24 hours post CPB. Post CPB, the stroke volume (SV) (p = 0.01), left ventricular stroke work (LVSW) (p = 0.005), left ventricular stroke work index (LVSWI) (p = 0.02) and cardiac output (CO) increased in Group B. Post induction, eNOS and Hsp72 in Group B were higher. Following IRI, eNOS and Hsp72 in Group A decreased while in Group B it increased. Post CPB, eNOS and Hsp72 in Group B remained higher. In Group B, eNOS post IRI positively correlated with LVSW (p=0.05) and LVSWI (p=0.006) 4 hours post CPB. Furthermore, in Group B, Hsp72 post IRI correlated positively with LVSWI post CPB (p=0.01) while Hsp72 post CPB correlated positively with LVSWI post CPB (p=0.01). Post CPB, in Group B, the increase in eNOS correlated with Hsp72 (p>0.05). This study clinically demonstrated that HBO preconditioning prior to IRI improves myocardial function following IRI. This cardioprotection occurs in association with increased myocardial expression of eNOS and Hsp72. This clinical study supports experimental findings which suggest that the mechanism for this cardioprotection may involve a dependent linkage between the expressions of eNOS and Hsp such as Hsp72.