Background: Appropriate use of diagnostic laboratory tests is challenging, and estimates of 20% for overutilization and 45% for underutilization have been reported. Introducing effective and sustainable solutions to stimulate optimal use of laboratory testing in clinical practice is a challenge. A recent pilot study from our group, focusing on increasing the awareness about appropriate laboratory testing with the aim of changing the mindset of health care workers, has shown promising results. In this project, we aim to extend this multistep intervention to the internal medicine departments of 4 large Dutch hospitals. We aim to reduce unnecessary laboratory testing by 5%. Objective: Our primary objective is to determine the effect of our intervention on diagnostic laboratory test order volume. Our secondary objectives are to determine the effect of our intervention on laboratory expenditure and order volumes, expenditures for other diagnostic modalities, and clinical patient outcomes. We will also analyze the barriers and facilitators for deimplementation of unnecessary laboratory testing. Methods: The main interventions of this before-after study will be an intensified supervision of residents by experienced physicians regarding test ordering, creating awareness through education and monthly feedback on ordering patterns, and changes in (computerized) order entry systems. Results: At the time of publication of this protocol, the project is in the phase of data collection. We expect to present data on reduction early in the fourth quarter of 2018. Conclusions: In this project, we aim to reduce the unnecessary diagnostic testing in the internal medicine departments of 4 teaching hospitals. Although the main interventions will be similar, each clinic is given the opportunity to focus on the specific facets of the interventions as deemed useful according to the local situation. If effective, the study provides a framework for a nationwide initiative for reducing inappropriate laboratory testing.