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Study purpose: This study aims to investigate the impact of CDSS on patient safety through the experiences of nursing staff. Methods: As the study intends to arrive at specific conclusions on the perceptions of nurses on the impact of CDSS on patients’ safety, a cross-sectional quantitative survey design is adopted in this study. The Hospital Survey of Patients’ Safety Culture (HSOPSC) was used in this study to assess the influence of CDSS on various factors of patient safety. A total of 473 nurses from eight hospitals in Saudi Arabia participated in this study. Results: The PRR of ‘team work within units’ was identified to be the highest (65.9%), followed by ‘hands-off and transitions’ (64.7%), ‘overall patents safety’ (64.1%), and ‘frequency of reports’ that were corrected (61.1%). Communication openness (27.9%) achieved the lowest PRR; while team work across units (2.82) achieved the lowest mean score. Conclusion: The CDSS needs to be integrated with other interventions that promote communication and develop a supportive and cooperative culture among the nurses for ensuring a positive patient safety culture in Saudi Arabian hospitals.