BACKGROUND: Long-term ventilator-dependent patients often face problems such as decreased quality of life, increased mortality, and increased medical costs. Respiratory therapists must perform complex and time-consuming ventilator weaning assessments, which typically take 48-72 hours. Traditional disengagement methods rely on manual evaluation and are susceptible to subjectivity, human errors, and low efficiency. OBJECTIVE: This study aims to develop an artificial intelligence-based prediction model to predict whether a patient can successfully pass a spontaneous breathing trial (SBT) using the patient's clinical data collected before SBT initiation. Instead of comparing different SBT strategies or analyzing their impact on extubation success, this study focused on establishing a data-driven approach under a fixed SBT strategy to provide an objective and efficient assessment tool. Through this model, we aim to enhance the accuracy and efficiency of ventilator weaning assessments, reduce unnecessary SBT attempts, optimize intensive care unit resource usage, and ultimately improve the quality of care for ventilator-dependent patients. METHODS: This study used a retrospective cohort study and developed a novel deep learning architecture, hybrid CNN-MLP (convolutional neural network-multilayer perceptron), for analysis. Unlike the traditional CNN-MLP classification method, hybrid CNN-MLP performs feature learning and fusion by interleaving CNN and MLP layers so that data features can be extracted and integrated at different levels, thereby improving the flexibility and prediction accuracy of the model. The study participants were patients aged 20 years or older hospitalized in the intensive care unit of a medical center in central Taiwan between January 1, 2016, and December 31, 2022. A total of 3686 patients were included in the study, and 6536 pre-SBT clinical records were collected before each SBT of these patients, of which 3268 passed the SBT and 3268 failed. RESULTS: The model performed well in predicting SBT outcomes. The training dataset's precision is 99.3% (2443/2460 records), recall is 93.5% (2443/2614 records), specificity is 99.3% (2597/2614 records), and F-score is 0.963. In the test dataset, the model maintains accuracy with a precision of 89.2% (561/629 records), a recall of 85.8% (561/654 records), a specificity of 89.6% (586/654 records), and an F-score of 0.875. These results confirm the reliability of the model and its potential for clinical application. CONCLUSIONS: This study successfully developed a deep learning-based SBT prediction model that can be used as an objective and efficient ventilator weaning assessment tool. The model's performance shows that it can be integrated into clinical workflow, improve the quality of patient care, and reduce ventilator dependence, which is an important step in improving the effectiveness of respiratory therapy.