Background: Clinical decision support systems (CDSSs) have gained prominence in health care, aiding professionals in decision-making and improving patient outcomes. While physicians often use CDSSs for diagnosis and treatment optimization, nurses rely on these systems for tasks such as patient monitoring, prioritization, and care planning. In nursing practice, CDSSs can assist with timely detection of clinical deterioration, support infection control, and streamline care documentation. Despite their potential, the adoption and use of CDSSs by nurses face diverse challenges. Barriers such as alarm fatigue, limited usability, lack of integration with workflows, and insufficient training continue to undermine effective implementation. In contrast to the relatively extensive body of research on CDSS use by physicians, studies focusing on nurses remain limited, leaving a gap in understanding the unique facilitators and barriers they encounter. Objective: This study aimed to explore the facilitators and barriers influencing the adoption and use of CDSSs by nurses in hospitals, using an extended Fit Between Individuals, Tasks, and Technology (FITT) framework. Methods: A qualitative study was conducted using semistructured interviews with 22 nurses from across the Netherlands, representing 3 hospital types: general (n=9), top-clinical (n=12), and academic (n=1). The sample included a diverse mix of practicing nurses, nurses-in-training, and clinical nurse information officers, with clinical experience ranging from 1.5 to 38 years. Interview transcripts were analyzed thematically, beginning with an inductive coding approach to identify key factors. These were then categorized deductively using the extended FITT framework. In total, 988 code instances were examined. To ensure analytical rigor, the coding process was separately conducted by 2 researchers and reviewed by an expert panel. Results: A total of 26 distinct factors were identified, categorized into 4 FITT dimensions: technology-individual, technology-task, task-individual, and organizational context. Of these, 11 factors were facilitators (eg, cognition, clarification, and prevention), 7 were barriers (eg, alarm fatigue, poor design, and limited digital proficiency), and 8 were both facilitators and barriers depending on the context (eg, acceptance, workload, and training). In addition, key value tensions emerged, such as the balance between standardization and professional autonomy, and the trade-off between enhanced decision support and increased administrative burden. Conclusions: The findings underscore the complexity of CDSS adoption in nursing practice, highlighting the interaction of facilitators and barriers across FITT dimensions. Practical recommendations include participatory design processes, targeted training programs, advanced alert management systems, and strong organizational support. Addressing value tensions and aligning CDSS functionality with nurses’ workflows can enhance adoption and optimize patient outcomes. Trial Registration:
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