Objective: The Clinical Decision Support System (CDSS) for drug prescriptions was developed by integrating the computerized physician order entry (CPOE) system to support doctors and pharmacists in making correct decisions on prescribing drugs in line with the prescription guidelines by the Health Insurance Review Agency (HIRA). The objective of this study was to evaluate the performance of the CDSS with respect to system quality, information quality, and user satisfaction in reducing prescription errors. Methods: The study was based on survey data from 38 hospitals that were using the CDSS for drug prescriptions. To identify factors influencing the performance of CDSS, multiple linear regression and chi-square analyses were performed. Results: Regression analysis showed that the variables for system quality and information quality significantly influenced the overall system performance. Specifically, ease of understanding the results and terminology assystem quality measures significantly influenced user satisfaction. Furthermore, based on chi-square analysis, two independent variables (ease of understanding results and decision support functions) were statistically significant with respect to all four dependent variables (information satisfaction, system satisfaction, willingness to recommend to other hospitals, and drug safety). Conclusion: Based on this study, users should be educated to improve their understanding of the system,and system and information quality should be continuously monitored to improve user satisfaction. (Journal of Korean Society of Medical Informatics 15-3, 293-301, 2009)