Abstract. Background: Osteopenia of prematurity is common among extremely low birth weight infants (ELBW). There arecurrently no standard practices regarding screening, prevention or treatment of this condition. Objective: To determine if introduction of a nutritional monitoring and interventional protocol would decrease the incidenceand severity of osteopenia of prematurity. Methods: A nutritional protocol to monitor the needs and provide supplementation of calcium and phosphorus has beeninstituted in our unit. We compared ELBW infants born in the year before (Group 1) vs. after (Group 2) for lowest serumphosphorus, peak alkaline phosphatase and bone fractures. Logistic regression analysis was used to determine the independenteffect of gestational age, birth weight, diuretics, postnatal steroids, and the nutritional protocol. Results: Osteopenia-related outcomes improved, including: phosphorus level <3 mg/dL 34% vs. 14%, (P = 0.003), peakalkaline phosphatase >750 IU/L 18% vs. 7%, (P = 0.018), and bone fractures 16.4% vs. 5.4%, (P = 0.026). The use of diureticsincreased significantly, while the use of postnatal steroids decreased significantly. Logistic regression analysis confirmed theindependent contribution of our nutritional protocol as well as birth weight to osteopenia of prematurity outcomes. Conclusions: This is the first study to report that initiation of a protocol for monitoring and optimizing bone mineralizationcan decrease the incidence of severe osteopenia of prematurity as manifested by hypophosphatemia, elevated ALP and bonefractures. Implementation of a neonatal intensive care clinical practice guideline will improve this largely preventable medicalcomplication.