BACKGROUND: Hazardous drug exposure is an occupational health hazard to oncology nurses. Sparse data are available regarding the frequency and characteristics of hazardous drug spills. OBJECTIVES: This article aims to describe nurses hazardous drug exposures and use of personal protective equipment during drug spills. METHODS: The Drug Exposure Feedback and Education for Nurses Safety study launched in March 2015. When drug spills occurred, consented RNs administering chemotherapy in ambulatory infusion settings completed brief questionnaires. Descriptive statistics were used to summarize equipment use and spill events. FINDINGS: Spills were common, despite the use of closed-system transfer devices. Over two years, 51 nurses from 12 participating academic infusion centers reported 61 unique spills. Spills commonly involved highly toxic drugs. Personal protective equipment use during drug spills was suboptimal. These foundational data reveal gaps in clinical practice.