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Rationale & Objective: Infection prevention efforts in dialysis centers can avert patient morbidity and mortality but are challenging to implement. The objective of this study was to better understand how the design of the work system might contribute to infection prevention in outpatient dialysis centers., Study Design: Mixed methods, observational study., Setting & Participants: Six dialysis facilities across the United States visited by a multidisciplinary team over 8 months., Analytical Approach: At each facility, structured macroergonomic observations were undertaken by a multidisciplinary team using the SEIPS 1.0 model. Ethnographic observations were collected about staff encounters with dialysis patients including the content of staff conversations. Selective and axial coding were used for qualitative analysis and quantitative data were reported using descriptive statistics., Results: Organizational and sociotechnical barriers and facilitators to infection prevention in the outpatient dialysis setting were identified. Features related to human performance, (eg, alarms, interruptions, and task stacking), work system design (eg, physical space, scheduling, leadership, and culture), and extrinsic factors (eg, patient-related characteristics) were identified., Limitations: This was an exploratory evaluation with a small sample size., Conclusions: This study used a systematic macroergonomic approach in multiple outpatient dialysis facilities to identify infection prevention barriers and facilitators related to human performance. Several features common across facilities were identified that may influence infection prevention in outpatient care and warrant further exploration., (Copyright © 2024 National Kidney Foundation, Inc. All rights reserved.)