Background: The proper decision-making on weaning patients from the ventilator, removing the endotracheal tube, reducing complications, and the way of cooperating between doctor and nurse is always one of the concerns of intensive care unit (ICU) nurses. Objectives: This study aimed to determine the effect of clinical decision-making based on interactive education on the successful extubations of patients in the ICU. Methods: This quasi-experimental study was conducted on 50 nurses in the ICU of Ganjavian Hospital in Dezful, Iran, within August-December 2021. The nurses were selected based on inclusion criteria and randomly assigned into intervention and control groups. Clinical decision-making training regarding extubation was provided interactively for one month in five sessions in the experimental group. The data were obtained using a demographic information questionnaire, the Clinical Decision-Making Questionnaire by Lauri et al., and extubation checklist and analyzed using SPSS software (version 24) using descriptive and inferential statistics (i.e., chi-square test, covariance, independent t-test, and paired t-test). Results: No difference was observed between the two groups in terms of demographic information (P < 0.05). After the intervention, the mean score of nurses’ clinical decisions and the number of successful extubations in the experimental group were higher than in the control group, with a statistically significant difference (P = 0.014). Conclusions: Interactive training effectively improves decision-making skills concerning successful extubations. Therefore, it is suggested to use this method in educational programs to improve the clinical decision-making of nurses, students, and nursing managers.