The Portland Diabetic Project is an ongoing prospective study of 5534 diabetic cardiac surgery patients that elucidates the effects of hyperglycemia, and its subsequent reduction with continuous insulin infusions (CII), on in-hospital outcomes. Increasing glucose levels were found to be directly associated with increasing rates of death, deep sternal wound infections (DSWI), length of stay (LOS), and hospital costs. In separate multivariable analyses, hyperglycemia was found to be independently predictive of mortality (P < 0.0001), DSWI (P = 0.0001), and LOS (P < 0.002). Conversely, CII, designed to achieve predetermined target glucose levels, independently reduced the risks of death and DSWI by 65% and 63%, respectively (P < 0.001 for both). Target glucose levels <150 mg/dL and a 3-day postoperative duration of CII therapy are both important variables that determine the impact of the CII therapy on improved outcomes. Perioperative hyperglycemia in cardiac surgery patients adversely alters mortality, LOS, and infection rates. CII eliminate the increased risks of these complications previously seen in diabetic patients. CII protocols are the standard-of-care for glycometabolic control in cardiac surgery patients.