Background: The hyperinsulinemic euglycemic clamp is the gold standard for assessment of insulin resistance and requires frequent, accurate measurements of blood glucose concentrations, typically utilizing the YSI 2300 STAT Plus™ glucose analyzer (YSI, Inc., Yellow Springs, OH). Despite its accuracy, the YSI has several limitations, including its cost, lengthy run time, need for trained personnel, frequent maintenance, and large blood volumes. Simpler hospital-grade hand-held glucose meters are now available but have not been validated for use in pediatric clamp settings. Our objective was to evaluate the accuracy, precision, and reliability of the StatStrip® (SS) hospital glucose monitoring system (Nova Biomedical, Waltham, MA) relative to the YSI 2300 STAT glucose analyzer in pediatric hyperinsulinemic euglycemic clamps. Subjects and Methods: Four hundred sixty blood specimens drawn from 11 pediatric patients undergoing hyperinsulinemic euglycemic clamps were simultaneously analyzed by SS and YSI. Outcome measures included SS bias relative to YSI and glucose measurement precision on SS and YSI. Results: The SS showed a slight positive bias of 0.75±2.83 mg/dL versus the YSI. Percentage coefficients of variance for SS and YSI were 9.53% and 9.25%, respectively. Using a Bland-Altman plot, the limits of agreement were ±5.7 mg/dL. The coefficient of repeatability for SS was 6.63; the coefficient of individual agreement between the YSI and SS was 0.995. Conclusions: The SS is a suitable replacement for the YSI in pediatric hyperinsulinemic euglycemic clamp studies, is easier to use, more cost-effective, and faster, and requires less blood. Future euglycemic clamp studies can consider utilizing this methodology.