Background: Oxygen is administered as a corrective treatment for conditions resulting in hypoxia (low level of oxygen in the blood). Oxygen therapy is most frequently used nursing procedure in developed and developing countries. However, there were significant practice gaps regarding oxygen therapy despite their frequent use. It is reported that maximum percent of oxygen delivery and flow rates are particularly poor, with potential negative impact on patient care including delivering too little oxygen in emergencies, leading to carbon dioxide retention. There is no study conducted about practice of oxygen therapy and associated factors in the study area particularly DMRH, TGSH,FHCRH, so this study will fill this gap. Objective: To assesspractice of oxygen therapy and its associated factors among nurses working in emergency and intensive care unit in West Amhara referral public hospitals, North West Ethiopia 2023. Methods:Facility based cross-sectional study design was conducted among 190 nurses from March 17 to May 4, 2023. Simple random samplings were employed and self-administered structured questionnaires, and observational check list was used to collect data. Data was edited and entered into EPI data version 4.6 and exported to SPSS version 27 for analysis. Binary and multiple logistic regression models were used to assess the association between predictors and practice of oxygen therapy. Significant independent variables were declared at 95% confidence interval and P-value of less than 0.05 as cut off point. Results: This study showed 36.8 % of nurses had a good practice on supplemental oxygen administration. Good attitude [AOR=5.84, 95 % CI (1.93, 17.63)],Female nurses [AOR=3.03, 95% CI (1.24-7.37)], training (AOR 7.9, 95% CI (2.87-21.71)]guideline of oxygen therapy and [3.61, 95% CI (1.59-8.16)] had significant associations on oxygen therapy. Conclusion and recommendation: oxygen therapy practice was low among nurses working in West Amhara referral hospitals. Attitude, training, sex, age and guideline of oxygen therapy were significant factors. Amhara health bureau should be consider expanding critical care medicine should engage in training practitioners and change nurses’ attitude specially who provide care for critically ill patients. KEY WORDS: Ethiopia, Nurse, Oxygen therapy, Practice