Background: Weaning from mechanical ventilation is a complex and central intensive care process. This complexity indicates that the challenges of weaning must be explored from different perspectives. Furthermore, physicians' experiences and the factors influencing their decision-making regarding weaning are unclear. Objectives: This study aimed to explore and describe the factors influencing physicians' decision-making when weaning patients from invasive mechanical ventilation in Swedish intensive care units (ICUs). Methods: This qualitative study used an exploratory and descriptive design with qualitative content analysis. Sixteen physicians from five ICUs across Sweden were purposively included and interviewed regarding their weaning experiences. Findings: The physicians expressed that prioritising the patient's well-being was evident, and there was agreement that both the physical and mental condition of the patient had a substantial impact on decision-making. Furthermore, there was a lack of agreement on whether patients should be involved in the weaning process and how their resources, needs, and wishes should be included in decision-making. In addition, there were factors not directly linked to the patient but which still influenced decision- making, such as the available resources and teamwork. Sometimes, it was difficult to point out the basis for decisions; in that decisions were made by gut feeling, intuition, or clinical experience. Conclusion: Physicians' decision-making regarding weaning was a dynamic process influenced by several factors. These factors were related to the patient's condition and the structure for weaning. Increased understanding of weaning from the physicians' and ICU teams' perspectives may improve the weaning process by broadening the knowledge about the aspects influencing the decision-making. (c) 2024 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).