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This study proposed an evaluation model, derived from the Technology Acceptance Model and Information System Success Model, to explore factors influencing the acceptance of hospital information systems by nurses. Although many healthcare institutions have applied hospital information systems, relatively few studies have investigated the perceptions of nurses regarding the usefulness, ease of use, or acceptance of these systems. This study recruited the nursing staff of a regional hospital in Taiwan. A total of 297 questionnaires were sent, and 277 were returned, for a response rate of 93.3%. The results indicated that system quality, information quality, and service quality were positively correlated with the perceived ease of use (R2= 0.69) and perceived usefulness (R2 = 0.72). Information quality has the greatest influence on perceived usefulness (γ3 = 0.57, P < .001) and ease of use (γ4 = 0.61, P < .001). Perceived usefulness and ease of use have a significant influence on system acceptance (R2 = 0.75). Perceived usefulness (β1 = 0.61, P < .001) has a significant influence on system acceptance. These findings indicated that nursing care requires high-quality healthcare information tosupport the daily activities of nursing professionals. The results of this study also provide a valuable reference for hospital administrators in developing hospital information systems.