Background: Research suggests that capturing the benefits of electronic health records (EHR) requires systematic and ongoing optimization of technology configuration and use after implementation. However, little is known about EHR optimization in a hospital context. Objective: To explore the issues and challenges involved in organizing and managing a systematic user-driven EHR optimization program. Methods: A longitudinal case study of an EHR optimization program launched in two large Danish hospital systems was undertaken. It involved interviewing 28 key managers, clinicians and IT staff, participating in formal and informal meetings, and reviewing policy documents, meeting minutes, teaching materials and other relevant documents. Findings: The two hospital systems are struggling to find the best way to organize and manage the optimization program. So far, the program has been a mixed success. Involving clinicians in EHR optimization poses serious dilemmas for hospital managers, who must manage two related tensions: between standardization and adaptation, and between centralized control and local autonomy. Conclusion: The findings highlight the significant challenges in designing a successful EHR optimization program and underscore the importance of developing more sophisticated strategies for clinical standardization and innovation.