In line with the global trend, hospitals in the Kingdom of Saudi Arabia, including tertiary medical care centers, have increasingly adopted comprehensive electronic medical record (EMR) systems in the past twenty years. However, knowledge of these systems and the extent of their impact on performance is still limited in the Kingdom due to the lack of studies researching in this field. Accordingly, this study aims to investigate the impact of implementing a comprehensive EMR system in King Abdullah Medical City (KAMC) on hospital performance and to test the assumed hypotheses which propose that implementing a comprehensive EMR significantly improves the clinical effectiveness, patient-centeredness, patients' safety and production efficiency in an advanced tertiary care setting in Saudi Arabia. To achieve this, a quantitative cross-sectional survey was conducted, using a valid questionnaire, on a random representative sample of 150 participants from healthcare professionals working in KAMC who experienced the upgrade towards the comprehensive EMR. The data collected was analyzed and the results showed the existence of statistically significant relationships between the implementation of comprehensive EMR as an independent variable and the four investigated dependent variables which are clinical effectiveness, patient-centeredness, patients' safety and production efficiency in an advanced tertiary care setting in Saudi Arabia at significance level p=0.000 < 0.05. The study concluded the necessity of implementing comprehensive EMR to the point where tertiary care hospitals should pay attention to the application of such advanced electronic system because of their role in improving health care performance. Eventually, the study recommends the need to build an integrated EMR system at the level of the Kingdom that ensures the safe exchange of information between hospitals and health national centers which would enhance the provision of more distinguished health service for each patient, increase administrative efficiency and reduce the use of traditional means of recording like paper.