Background. Regional myocardial acidosis in patients undergoing cardiac surgery has been shown to be reflective of regional myocardial ischemia. This study elucidates the relationship between intraoperative regional myocardial acidosis and 30-day postoperative outcomes after cardiac surgery. Methods. Intramyocardial tissue pH in the anterior and posterior left ventricular walls was measured in 397 adult patients undergoing valve replacement or coronary revascularization surgery between 1987 and 2001. Dedicated nurses and research assistants prospectively collected preoperative, intraoperative, and outcomes data. Regional myocardial acidosis was defined in terms of pH thresholds identified by recursive partitioning. Adverse 30-day outcome, defined as death or any one of six complications, was the dependent variable in a multivariate logistic regression analysis. A morbidity score was developed on the basis of the sensitivity of each of the six complications in predicting death, and was the dependent variable in a multivariate linear regression analysis. Results. During the period of aortic clamping, a mean intramyocardial tissue pH less than 6.85 was identified to be significant by recursive partitioning, and was encountered in either the anterior or posterior left ventricular wall in 85.4% of patients. After adjusting for preoperative and intraoperative variables, this pH threshold was found to be significantly associated with increased adverse outcomes within 30 days after surgery (p = 0.045). It was also significantly associated with increase in the morbidity score (p = 0.05). Conclusions. Regional myocardial acidosis of a magnitude frequently encountered during aortic clamping is an independent determinant of adverse 30-day outcomes after cardiac surgery. Its reversal by pH-guided myocardial management has the potential of improving postoperative patient outcomes.