Objective: This study investigates the key factors affecting the acceptance of hospital information systems (HIS) by physicians based on an extensive technology acceptance model. This model consists of six constructs: System quality, information quality, service quality, perceived usefulness, perceived ease of use, and HIS acceptance. Materials and Methods: Survey research targeted physicians in the selected case hospital as subjects. Of 131 questionnaires sent out, 81 completed forms were returned (a valid response rate of 64.8%). The partial least squares approach was used to analyze the collected data. Results: This study shows that system quality and information quality are significant factors influencing perceived ease of use of HIS, while information quality and service quality are key factors affecting perceived usefulness of HIS. Results indicate that perceived usefulness and perceived ease of use significantly affect HIS acceptance (R-2 = 0.545) from the physician's perspective. Conclusions: The findings of this study can help managers understand the key considerations affecting HIS development and use and provide important reference material for system improvement.