Background: Poisoning is a major health issue worldwide. Nurses are frequently the first healthcare professionals to come in contact with patients with acute poisoning. So, this study was conducted to assess the knowledge and awareness regarding the management of acute poisoning among nurses. In case of insufficient knowledge, they could be trained enough to manage any case of acute poisoning for life-saving purposes.Methodology: This was a cross-sectional analytical study conducted among 212 nurses at Rajendra Institute of Medical Sciences, Ranchi, Jharkhand from July 2021 to December 2021. Data were collected using the structured questionnaire based on a previous study and regression analysis was used for determining the association between their overall knowledge score and independent variables like age, education, experience, and training status.Results: More than one-third (43.8%) of the study participants had an unsatisfactory level of knowledge, which might be because of a lack of proper training and experience, but still, 42.4% and 13.6% of the study participants had satisfactory and good knowledge, respectively. Moreover, more than one-third (45.2%) of the study participants had inefficient skills, while 48.1% and 6.6% of nurses had satisfactory and good skills, respectively, in the management of acute poisoning. The three independent variables (training, experience, and education) showed a 53.1% association with total scores in bivariate regression analysis while no significant association was seen between age and score in multivariate analysis.Conclusions: About half of the nurses showed unsatisfactory knowledge, so they need improvement and they should be trained regarding this to reduce mortality among acute poisoning cases.