Background: The economic consequences of interventions to promote rational, evidence-based use of laboratory tests by physicians are not yet fully understood. We evaluated the cost consequences of a computer-based, guideline-driven decision-support system (CDSS) for ordering blood tests in primary care. Methods: We installed the CDSS in 118 practices [159 general practitioners (GPs)] throughout The Netherlands and calculated the costs of the intervention in this group. During a period of 6 months before and 6 months after installation of the CDSS, the test-ordering behavior of 87 (109 GPs) of these 118 study practices was studied and the results were compared with those of a nonhistorical control group that did not receive the CDSS. In addition the costs of laboratory requests were calculated for both groups. Results: Total intervention costs, comprising development costs and installation costs, amounted to €79 000 (€670 per practice). Whereas the introduction of the CDSS did not affect the number of order forms submitted to the laboratories, it did reduce the number of blood tests per order form. As a result, the CDSS yielded mean savings on the costs of laboratory requests of €847 per practice per 6 months. Conclusions: This study demonstrates that providing electronic decision support for ordering blood tests in primary care represents an economically promising concept. Savings on laboratory costs are achievable and not offset by disproportionally high intervention costs.