Objectives: Adherence by oncology nurses to chemotherapy safe handling guidelines is essential to prevent hazards of chemotherapy exposure. A review of the literature revealed the need for an instrument with evi-dence of reliability and validity to measure factors influencing adherence to safe chemotherapy-handling guidelines among oncology nurses. The purpose of this study was to psychometrically test the Oncology Nurses' Health Behaviors Determinants Scale (HBDS-ON) that measures the mentioned factors. Data Sources: Methodological research of a quantitative cross-sectional survey design was used. The study surveys were administered by email to a sample of 108 oncology nurses. Cronbach alpha, item analysis, exploratory factor analysis using principal axis factoring, and convergence validity testing were used to test reliability and validity.Conclusion: Factor analysis yielded six subscales, each having acceptable internal consistency reliability (Cronbach alpha between 0.70 and 0.88). The subscales included four oncology nurse health beliefs (per-ceived threat, benefits, barriers, and self-efficacy), cues to action, and personal protective equipment avail-ability and accessibility. Convergence validity testing results support the Oncology Nurses Health Behaviors Determinant Scale (HBDS-ON) construct validity. Oncology nurses' self-efficacy to adherence to chemother-apy-handling guidelines, the perceived barriers to adhere to chemotherapy-handling guidelines, and cues to action are associated with adherence to chemotherapy-handling guidelines. Implications for Nursing Practice: Oncology nurses' health beliefs, the cues to action, and personal protection equipment availability and accessibility are important determinants of nurses' adherence to chemotherapy -handling guidelines. The HBDS-ON is an instrument that has evidence of reliability and validity and could be used in practice to measure these determinants.(c) 2023 Elsevier Inc. All rights reserved.