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Objectives: To determine the effect of iterative refinement of standard ordering protocols on test utilization and results for bone marrow biopsy specimens.Methods: Eighteen months of test utilization and result data were used to revise the protocols that determine cytogenetic and molecular test selection on bone marrow specimens and then compared with data obtained following protocol revision.Results: Revision of protocols resulted in reduction in total tests and associated charges, due to a decrease in tests both concordant and discordant with the protocols. These reductions only occurred in diseases for which revisions were made and were limited to cases in which reflex testing was performed. There was an increase in the fraction of positive tests, which was also limited to reflex testing.Conclusions: Data-driven iterative revision of protocols further improves test utilization and performance, while reducing cost. Analysis of testing data can be used to continuously improve test ordering decisions.