The ability of retrograde warn blood cardioplegia to preserve hypertrophied myocardium remains controversial. This two-part study was undertaken to address this question in patients subjected to aortic valve replacement for calcified aortic valve stenosis complicated with echocardiographically defined left ventricular hypertrophy. Part I was designed to assess the intraoperative patterns of myocardial oxidative metabolism in 20 patients in whom the severity of left ventricular hypertrophy was reflected by a mean (± standard error of the mean) myocardial mass index of 213 ± 15 g/m2. After antegrade arrest, warm blood cardioplegia was continuously given through the coronary sinus at a flow rate of 200 ± 5 mL/min. The use of a low-dilution cardioplegia delivery technique enabled us to keep hematocrit at 25.6% ± 0.9% and the care temperature was allowed to drift to 32.7 ± 0.2 °C. At the end of the arrest period, blood samples were simultaneously taken from inflow (coronary sinus catheter) and outflow (left coronary ostium) cardioplegia and assayed for blood gases, oxygen content and saturation and lactate. Part II was designed to compare the clinical outcomes of these 20 warm patients with those of 20 case-matched patients in whom a conventional hypothermic myocardial protection technique was used. The results of part I show that after an average arrest period of 72 ± 4 minutes, the residual oxygen demand was still high as reflected by a percent oxygen extraction of 34.8% ± 4.1%. This demand, however, was adequately met by the supply, as demonstrated by (1) the absence of transmyocardial acid production, (2) a negligible release (outflow minus inflow) of lactate (0.28 ± 0.1 mmol/L), and (3) a high residual oxygen saturation (65.7% ± 3.8%) in outflow cardioplegia. The results of part II show that the clinical outcomes of warm patients were overall good and not different from those of the cold group. We conclude that retrograde warm blood cardioplegia can adequately preserve hypertrophied myocardium by keeping its metabolism predominantly aerobic during aortic cross-clamping provided that measures are taken to optimize the determinants of the oxygen demand/supply ratio throughout. These measures include avoidance of left ventricular distention, immediate ablation of any recurring activity during arrest, maintenance of high retrograde flow rates, limitation of hemodilution, and uninterrupted mode of cardioplegia delivery. © 1994.