AIM: To explore barriers and enablers of recognition and response to signs of patient deterioration by nursing staff in an acute hospital. DESIGN: A theory-driven interview study underpinned by the Theoretical Domains Framework of behaviour change. METHODS: Between 07/01/2019 and 18/12/2019 a purposive sample of registered nurses and healthcare assistants was recruited to participate in a semi-structured (audio-recorded) interview, to explore the determinants of seven specified behaviours of the afferent limb. Anonymised transcripts were deductively coded (using the 14 Theoretical Domains Framework domains as coding categories) and then extracts within each domain were inductively analysed to synthesise belief statements and themes. Prioritisation criteria from published literature were applied. RESULTS: Thirty-two semi-structured interviews were conducted. From 1,888 quotes, 184 belief statements and 66 themes were synthesised. One hundred and forty-six belief statements, represented by 58 themes, met prioritisation criteria. Nine domains of the Theoretical Domains Framework were of high importance: Knowledge; Social, Professional Role and Identity; Beliefs about Consequences; Reinforcement; Intentions; Goals; Memory, Attention and Decision Processes; Environment, Context and Resources and Social Influences. CONCLUSIONS: Barriers and enablers most likely to impact on nursing staff afferent limb behaviour were identified in nine domains of the Theoretical Domains Framework.