Purpose: Neonates who require Extracorporeal Membrane Oxygenation (ECMO) are at risk for calcium derangements and associated adverse outcomes. A large children’s hospital in the Southwest changed their practice from using calcium gluconate in priming their neonatal ECMO to using calcium chloride. The impact of this change was not investigated. Methods: A retrospective chart review of 56 neonates who required ECMO support one year prior to and one year following the practice change was conducted. Descriptive data was collected along with the first ionized calcium measured following ECMO initiation. Results: Upon review of the data, the post-ECMO calcium levels were not significant between the calcium gluconate and calcium chloride groups using a Mann Whitney U test (U = 315.5, z = -1.25, p = .213). However, a Chi-square test was significant (χ2(1) = 4.94, p = .026) for having calcium values outside of a normal range in the calcium gluconate group. Fisher’s exact test revealed an odds ratio of 3.43 for the first calcium being outside normal range in the calcium gluconate group. Implications: While comparison of the first measured ionized calcium post-ECMO between the two groups was not statistically significant, there was a significant correlation with normal post-ECMO calcium in the calcium chloride group. This suggest that both calcium gluconate and calcium chloride are appropriate for use in priming the neonatal ECMO circuit, however calcium chloride may provide tighter control of calcium during ECMO initiation in neonates.