Although the federal government’s Meaningful Use electronic health record (EHR) implementation program resulted in some successes, there have been many challenges. The purpose of this study was to obtain detailed empirical data to better understand physicians’ and nurses’ experiences with EHRs. We conducted in-depth interviews with 30 physicians and nurses from two large health systems that were focused on attaining Stage 3 Meaningful Use criteria. Thematic framework analysis identified themes related to perceived benefits and challenges with EHR use. Participants appreciated benefits such as real-time patient data and easier access to information. Challenges included lack of interoperability across units, and this seemed to underlie many other noted challenges such as increased workload, insufficient training, and the perceived need for workarounds. Two key findings included mixed messages about trust in the EHR’s information and its interference with interpersonal relationships. Results suggest that conservation of resources theory may be a useful strategy for understanding behaviors that enhance or undermine effective EHR use. Implications for policy and practice are discussed.