OBJECTIVES: A recent study at our institution indicated that 12.8% of all prescribed doses of venous thromboembolism (VTE) prophylaxis are not administered, with some nursing units approaching 30%.  Our goal was to assess nursing beliefs and practices related to non-administration of ordered VTE prophylaxis doses. METHODS: We conducted a mixed-methods study, including qualitative observation and quantitative survey assessment. The study was conducted on twelve inpatient nursing units with disparate non-administration rates of ordered VTE prophylaxis doses of either unfractionated heparin or enoxaparin.  Qualitative aspects of the nurse-patient encounter were directly observed by the lead investigator at the scheduled administration time of VTE prophylaxis until thematic saturation was achieved. A survey was distributed to all nurses on the included floors to identify beliefs and practices regarding non-administration of ordered VTE prophylaxis doses.  RESULTS: Low-performing units had an average pharmacologic VTE prophylaxis non-administration rate of 18%, compared to the high-performing units which averaged a non-administration rate of 10%.  During observations, some nurses presented pharmacologic VTE prophylaxis to their patients as an optional therapy and entered into negotiations with their patients whereby patients could promise to walk to avoid a dose.  Nurses on low-performing units were more likely to respond that VTE prophylaxis was prescribed for patients who do not require it (83% vs. 62%, p<0.0001) and were also more likely to believe that they had the clinical decision-making skills to determine when to omit unnecessary doses of prescribed VTE prophylaxis (80% vs. 50%, p<0.0001).  Workload was not identified as a reason for non-administration on either high- or low-performing units. CONCLUSIONS: Nurses on low-performing units more often believe they have the skills to determine which patients require pharmacologic VTE prophylaxis and are more likely to present the medication as optional to patients.  Strategies to improve administration rates should incorporate these findings.