Background Glycemic control in critically ill patients decreases infection and mortality. While capillary blood glucose values are accurate in normotensive patients and correlate with arterial samples, patients on vasopressors have altered peripheral perfusion that may affect accuracy of capillary blood glucose values tested using point of care devices. Objectives To compare capillary and arterial blood samples using point of care testing (POCT) with arterial blood samples using the clinical chemistry lab in patients following cardiothoracic surgery, and to determine if vasopressor medications or diminished peripheral perfusion influenced the accuracy of POCT values. Methods In a prospective, convenience sample (n=50) of adult post-operative cardiothoracic patients on insulin and vasopressors, samples (n=162) were obtained simultaneously from capillary and arterial sites during insulin infusion and tested on both POCT and clinical chemistry lab, respectively. Quality of peripheral perfusion was recorded using a standardized scale. Clarke error grid analysis and ISO 15197 were used to analyze the level of agreement between the three samples. Two-way ANOVA was used to analyze differences in blood glucose values with respect to vasopressor use and peripheral perfusion. Results An unacceptable level of agreement was found between the capillary POCT and arterial samples tested in the clinical chemistry lab (only 88.3% of values fell in Zone A, or within the ISO 15197 tolerance bands). Arterial POCT showed 94.4% agreement with the clinical chemistry lab. Vasopressor use demonstrated a statistically significant effect on the accuracy of arterial blood glucose values (F=15.01; p= .0001). Conclusions Capillary POCT is not within acceptable limits of agreement with the clinical chemistry lab. Even when using the more accurate arterial blood with POCT, patients with >2 vasopressors demonstrate significantly less accuracy as compared to patients on fewer vasopressors. Using the clinical chemistry lab may be safer for insulin titration in these patients.