Objective: In patients undergoing cardiac surgery, intraoperative myocardial acidosis, which quantifies regional myocardial ischemia, has been shown to increase the risk of adverse postoperative outcomes. In this study, we sought to determine the course of intraoperative myocardial acidosis and its impact on postoperative survival in patients with diabetes mellitus undergoing cardiac surgery. Methods: Intraoperative myocardial tissue pH37C was continuously measured in the anterior and posterior left ventricular walls in 264 patients undergoing cardiac surgery; 74 (28.0%) of the patients had diabetes (insulin-dependent diabetes: 54%; non-insulin dependent diabetes: 46%). The shortest time required to reach intraoperative myocardial tissue pH < 6.34 during aortic occlusion and > 6.73 during reperfusion were compared in 3 patient groups: insulin-dependent, non-insulin dependent, and nondiabetic. These pH thresholds have been demonstrated to be associated with adverse postoperative long-term survival. Results: The median times to reach intraoperative myocardial tissue pH37C < 6.34 during aortic occlusion were 14, 23, and 36 minutes in the insulin-dependent, non-insulin dependent, and non-diabetic groups, respectively (P = .003). The time taken to reach intraoperative myocardial tissue pH37C > 6.73 during reperfusion was similar between the 3 groups. After adjusting for relevant pre- and intraoperative parameters, the risk of developing intraoperative myocardial tissue pH < 6.34 during aortic occlusion was 73% higher in patients with insulin-dependent diabetes mellitus (P = .022) but the same in with patients with non-insulin dependent diabetes mellitus (P = .98) when compared with patients without diabetes. Patients with insulin-dependent diabetes mellitus also had nearly threefold decrease in long-term survival compared with that of patients without diabetes (P = .0007). Conclusions: Patients with insulin-dependent diabetes mellitus undergoing cardiac surgery are at a greater risk of developing intraoperative myocardial acidosis/ischemia and of decreased survival postoperatively compared with patients without diabetes.