Background: Infusion of high-osmolarity parenteral nutrition (PN) formulations into a peripheral vein will damage the vessel. In this study, the authors developed a refractometric method to predict PN formulation osmolarity for patients receiving PN. Methods: Nutrients in PN formulations were prepared for Brix value and osmolality measurement. Brix value and osmolality measurement of the dextrose, amino acids, and electrolytes were used to evaluate the limiting factor of PN osmolarity prediction. A best-fit equation was generated to predict PN osmolarity (mOsm/L): 81.05 x Brix value -116.33 (R-2 > 0.99). To validate the PN osmolarity prediction by these 4 equations, a total of 500 PN admixtures were tested. Results: The authors found strong linear relationships between the Brix values and the osmolality measurement of dextrose (R-2 = 0.97), amino acids (R-2 = 0.99), and electrolytes (R-2 > 0.96). When PN-measured osmolality was between 600 and 900 mOsm/kg, approximately 43%, 29%, 43%, and 0% of the predicted osmolarity obtained by equations 1, 2, 3, and 4 were outside the acceptable 90% to 110% confidence interval range, respectively. When measured osmolality was between 900 and 1,500 mOsm/kg, 31%, 100%, 85%, and 15% of the predicted osmolarity by equations 1, 2, 3, and 4 were outside the acceptable 90% to 110% confidence interval range, respectively. Conclusions: The refractive method permits accurate PN osmolarity prediction and reasonable quality assurance before PN formulation administration. (JPEN J Parenter Enteral Nutr. 2011; 35: 412-418)