Background: The Ministry of Health Malaysia invested significant resources to implement an electronic health record (EHR) system to ensure the full automation of hospitals for coordinated care delivery. Thus, evaluating whether the system has been utilized effectively is necessary, particularly on how it predicts the work performance of the health care providers. Methods: Convenience sampling was employed for data collection in three government hospitals for seven months. A standardized effectiveness survey for EHR systems was administered to health care providers (specialists, medical officers, and nurses) as they participated in medical education programs. Power analysis was conducted before and after the study to ensure adequate sample sizes and sufficient power. The empirical data was assessed by employing partial least squares-structural equation modeling for hypotheses testing. Results: As a results, knowledge quality had the highest score in predicting performance and had a large effect size, whereas system compatibility became the strongest component of system quality. The findings indicated that EHR systems supported the clinical tasks and workflows of care providers, which increased system quality, whereas increased quality of knowledge improved user performance. Conclusion: Therefore, knowledge quality and effective use should be incorporated into the evaluation study of EHR system effectiveness in health institutions. Data mining feature can be integrated into current systems for generating health populations and disease trend analysis easily and systematically, therefore improving clinical knowledge of care providers and effective use to maintain their productivity. The validated survey instrument can be further tested with empirical surveys in other public and private hospitals with different interoperable EHR systems.