Aims and objectives: To explore nurses' decision‐making regarding intravenous administration set replacement for vascular access device infusions in paediatric and adult clinical settings.

Background: Intravenous administration sets are routinely replaced at regular intervals in clinical practice with the goal of preventing catheter‐related bloodstream infection; however, emerging evidence is challenging traditional hang‐time durations. Nurses' perceptions and contextual factors affecting decision‐making for administration set replacement have not been assessed previously.

Design: Qualitative study using focus groups with contextualism methodology and inductive analysis.

Method: During November–December 2016, eight semi‐structured focus groups were conducted with 38 nurses at two metropolitan hospitals in Queensland, Australia. Interviews were audio‐recorded and transcribed. Two authors independently reviewed transcripts and extracted significant statements using Braun and Clarke's 7‐step method of thematic analysis. The COREQ checklist provided a framework to report the study methods, context, findings, analysis and interpretation.

Results: Five key themes emerged from the analysis: (a) infection prevention, (b) physical safety, (c) patient preference, (d) clinical knowledge and beliefs, and (e) workload. Administration set replacement can be a complex task, particularly when patients have multiple infusions and incompatible medications. Nurses drew on perceptions of patient preference, as well as previous experience, knowledge of peer experts and local policies, to aid their decisions.

Conclusions: Nurses use clinical reasoning to balance patient safety and preferences with competing workplace demands when undertaking administration set replacement. Nurses rely on previous experience, hospital and medication manufacturer policies, and peer experts to guide their practice.