Background: Early parenteral nutrition (PN) provides essential macro- and micronutrients for extremely low birth weight (ELBW) infants <1000 g. Frequent cases of hypercalcemia [whole blood ionized calcium (iCa) > 1.45 mmol/LI in the first week of life while receiving PN solutions at our large quaternary center prompted investigation and 2 plan-do-study-act (PDSA) cycles to reduce rates of hypercalcemia.Objective: We compared 2 cohorts of ELBW infants separated by PDSA cycles to evaluate and reduce the incidence of abnormal iCa concentration.Methods: Data were recorded for 150 premature infants with mean birth weight of 726 +/- 164 g, 48% male, and mean gestational age of 26 +/- 2.1 wk. This process included an internal practice analysis and PDSA cycles monitored prospectively over 3 y. From December 2011 to September 2012, 66 infants received 0-1.2 mmol parenteral phosphorus supplementation/(kg.d) beginning at 72 h of life. In the second protocol, 84 infants born September 2012 to July 2013 received earlier phosphorus supplementation within 24 h of life. The peak whole blood iCa and serum phosphorus concentrations in the first week of life were monitored.Results: Early introduction of phosphorus was significantly associated with a decreased mean peak iCa (1.64 +/- 0.27 mmol/L to 1.50 +/- 0.23 mmol/L, P = 0.001), and the incidence of severe hypercalcemia (iCa > 1.60 mmol/L) decreased from 50.0% to 21.4% (P = 0.002) in the first week of life. There was no difference in mortality, bronchopulmonary dysplasia, renal calcifications, seizures within 7 d of birth, brain calcifications, or intracranial hemorrhage between cohorts.Conclusion: Early introduction of phosphorus in PN solutions is associated with reduced incidence of whole blood iCa abnormalities in the first week of life and should be considered for ELBW infants. Ongoing evaluation of optimal mineral provision to this population after birth should be performed.