Aims and objectives: To identify that workarounds (defined as “informal temporary practices for handling exceptions to normal procedures or workflow”) by nurses using information technology potentially compromise medication safety. Therefore, we aimed to identify potential risk factors associated with workarounds performed by nurses in Barcode-assisted Medication Administration in hospitals. Background: Medication errors occur during the prescribing, distribution and administration of medication. Errors could harm patients and be a tragedy for both nurses and medical doctors involved. Interventions to prevent errors have been developed, including those based on information technology. To cope with shortcomings in information technology-based interventions as Barcode-assisted Medication Administration, nurses perform workarounds. Identification of workarounds in information technology is essential to implement better-designed software and processes which fit the nurse workflow. Design: We used the data from our previous prospective observational study, performed in four general hospitals in the Netherlands using Barcode techniques, to administer medication to inpatients. Methods: Data were collected from 2014–2016. The disguised observation was used to gather information on potential risk factors and workarounds. The outcome was a medication administration with one or more workarounds. Logistic mixed models were used to determine the association between potential risk factors and workarounds. The STROBE checklist was used for reporting our data. Results: We included 5,793 medication administrations among 1,230 patients given by 272 nurses. In 3,633 (62.7%) of the administrations, one or more workarounds were observed. In the multivariate analysis, factors significantly associated with workarounds were the medication round at 02 p.m.–06 p.m. (adjusted odds ratio [OR]: 1.60, 95% CI: 1.05–2.45) and 06 p.m.–10 p.m. (adjusted OR: 3.60, 95% CI: 2.11–6.14) versus the morning shift 06 a.m.–10 a.m., the workdays Monday (adjusted OR: 2.59, 95% CI: 1.51–4.44), Wednesday (adjusted OR: 1.92, 95% CI: 1.2–3.07) and Saturday (adjusted OR: 2.24, 95% CI: 1.31–3.84) versus Sunday, the route of medication, nonoral (adjusted OR: 1.28, 95% CI: 1.05–1.57) versus the oral route of drug administration, the Anatomic Therapeutic Chemical classification-coded medication “other” (consisting of the irregularly used Anatomic Therapeutic Chemical classes [D, G, H, L, P, V, Y, Z]) (adjusted OR: 1.49, 95% CI: 1.05–2.11) versus Anatomic Therapeutic Chemical class A (alimentary tract and metabolism), and the patient–nurse ratio ≥6–1 (adjusted OR: 5.61, 95% CI: 2.9–10.83) versus ≤5–1. Conclusions: We identified several potential risk factors associated with workarounds performed by nurses that could be used to target future improvement efforts in Barcode-assisted Medication Administration. Relevance to clinical practice: Nurses administering medication in hospitals using Barcode-assisted Medication Administration frequently perform workarounds, which may compromise medication safety. In particular, nurse workload and the patient–nurse ratio could be the focus for improvement measures as these are the most clearly modifiable factors identified in this study.