Abstract
<title>Abstract</title> <p>Introduction The integration of artificial intelligence into healthcare is a significant promise for improving patient outcomes and enhancing the efficiency of clinical operations. However, the successful implementation of AI-based Clinical Decision Support System largely depends on the readiness and acceptance of healthcare professionals. Objective The aim of this study was to assess readiness and associated factors to use AI-based Clinical Decision Support System among Healthcare Professionals at the University of Gondar Comprehensive Specialized Hospital, Ethiopia, 2025. Methods An institution-based cross-sectional study supplemented with qualitative data was conducted. A total of 423 healthcare professionals were selected by a simple random sampling method for quantitative study, while 7 participants were selected for qualitative study using purposive sampling and key informant interviews were used. Bi-variable and multi-variable logistic regression analyses were used. To ascertain association, an odds ratio with a 95% confidence interval was used to declare statistical significance at a p-value of less than 0.05. Qualitative data were analyzed thematically. Result Out of 423 invited participants, 410 responded, yielding a 97% response rate. The overall readiness level for adopting AI-based CDSS was 50.5% (95% CI: 45.5%–55.4%). Profession, educational level, years of work experience, and ownership of a personal computer were significantly associated with readiness. Physicians, highly educated professionals, and those who owned computers were more likely to demonstrate higher readiness. Qualitative findings revealed facilitators such as perceived usefulness and potential to improve patient care. Barriers included limited digital literacy, inadequate infrastructure, and concerns about job displacement. Conclusion Approximately half of healthcare professionals demonstrated adequate readiness for AI-based CDSS adoption. Strengthening digital literacy, improving access to computers, enhancing self-efficacy, promoting positive attitudes and raising awareness about AI benefits are essential to improve readiness for implementation in this setting.</p>