Ethyl diazoacetate is an important organic chemistry synthon, but its use as an industrial intermediate is limited due in part to the safety concerns associated with its instability and high reactivity. Reported are the reaction calorimetry results obtained from a new ethyl diazoacetate preparative method, the results from its use in a novel, exothermic reaction and the application of this data toward process development, a successful pilot plant campaign and full-scale reactor design. The results indicate that, given the proper engineering design, in situ preparation and use of ethyl diazoacetate solutions can be used at production scale without significant risk.