Background: Point-of-care (POC) glucometers are commonly used in intensive care units (ICUs). The Centers for Medicare & Medicaid Services have called into question the accuracy of POC glucometers in critically ill patients. This study sought to identify specific characteristics within our facility’s ICU patients that were associated with inaccuracies in POC glucose measurements. Methods: We conducted a prospective cohort study that compared POC capillary blood glucose samples with venous samples collected in our ICU. All nonpregnant patients >18 years old admitted to the ICU with orders for daily laboratory testing that included blood glucose were eligible for inclusion. Results: A total of 46 patients were enrolled and 85 samples were collected. The mean difference between venous and POC samples was 5.23 mg/dL (95% CI, 3.16-7.3 mg/dL). Measurement inaccuracies would have altered treatment in 7/85 instances (8.2%). The only clinically significant inaccuracy found was the omission of 2 units of insulin in 1 hyperglycemic patient. Measurement inconsistencies generally underestimated low blood glucose values (2/2 instances) and overestimated high blood glucose values (4/5 instances). Conclusions: In our study, the mean difference between venous and POC glucose samples was small. Similarly, measurement inaccuracies that would have altered treatment were rare and only one instance was deemed clinically significant. We conclude that POC capillary glucose testing within our cohort and in similar critically ill patients is likely safe and effective.