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Cardiothoracic intensive care unit (CICU) nurses have shared the role and responsibility for ventilator-weaning to expedite decision-making in patient care. However, the actions taken are based on individual's unstructured training experience as there is no clinical practice guideline (CPG) for nurses in Malaysia. Hence, this study aims to design a CPG for the process of weaning from mechanical ventilation (MV) for a structured nursing training in a CICU at the National Heart Institute (Institut Jantung Negara, IJN) Malaysia. The Fuzzy Delphi Method (FDM) was employed to seek consensus among a panel of 30 experts in cardiac clinical practice on the guidelines. First, five experts were interviewed and their responses were transcribed and analyzed to develop the items for a FDM questionnaire. The questionnaire, comprising of 73 items, was distributed to the panel and their responses were analyzed for consensus on the design of the CPG. The findings suggested that the requirements expected for the nurses include: (a) the ability to interpret arterial blood gases, (b) knowledge and skills on the basics of mechanical ventilation, and (c) having a minimum 1-year working experience in the ICU. On the other hand, the CPG should mainly focus on developing an ability to identify criteria of patient eligible for weaning from MV. The learning content should focus on: (a) developing the understanding and reasoning for weaning and extubating and (b) technique/algorithm for extubating and weaning. Also, the experts agreed that the log book/competency book should be used for evaluation of the program. The CPG for structured nursing training at IJN in the context of the study is important for developing the professionalism of CICU nurses in IJN and could be used for training nurses in other CICUs, so that decision for ventilator-weaning from postcardiac surgery could be expedited.