Paramount to patient safety is the ability for nurses to make clinical decisions free from human error. Yet, the dynamic clinical environment in which nurses work is characterized by uncertainty, urgency, and high consequence, necessitating that nurses make quick and critical decisions. The aim of this study was to examine the influence of human and environmental factors on the decision to administer among new graduate nurses in response to alert generation during bar code–assisted medication administration. The design for this study was a descriptive, longitudinal, observational cohort design using EHR audit log and administrative data. The study was set at a large, urban medical center in the United States and included 132 new graduate nurses who worked on adult, inpatient units. Research variables included human and environmental factors. Data analysis included descriptive and inferential analyses. This study found that participants continued with administration of a medication in 90.75% of alert encounters. When considering the response to an alert, residency cohort, alert category, and previous exposure variables were associated with the decision to proceed with administration. It is important to continue to study factors that influence nurses' decision-making, particularly during the process of medication administration, to improve patient safety and outcomes.