Background: Although the prescription of physical activity in clinical care has been advocated worldwide, in the Netherlands, “Exercise is Medicine” (E = M) is not yet routinely implemented in clinical care. Methods: A set of implementation strategies was pilot implemented to test its feasibility for use in routine care by clinicians in 2 departments of a university medical center. An extensive learning process evaluation was performed, using structured mixed methods methodology, in accordance with the Reach, Effect, Adoption, Implementation, and Maintenance framework. Results: From 5 implementation strategies employed (education, E = M tool embedded in the electronic medical records, lifestyle coach situated within the department, overviews of referral options, and project support), the presence of adequate project support was a strong facilitator of the implementation of E = M. Also, the presence of the lifestyle coach within the department seemed essential for referral rate. Although clinicians appreciated the E = M tool, barriers hampered its use in practice. Conclusions: Specific implementation strategies, tailored to the setting, are effective in facilitating the implementation of E = M with specific regard to education for clinicians on E = M, deployment of a lifestyle coach within a department, and project coordination. Care providers do see a future for lifestyle coaches who are structurally embedded in the hospital, to whom they can easily refer.