Abstract Background Extubation is a critical step in the intensive care unit (ICU). In this study, we aim to investigate the risk factors for both extubation failure and deterioration with further mechanical ventilation (MV). Methods Data were collected from a cardiothoracic ICU in a tertiary hospital. The risk factors for extubation failure and deterioration with further MV were investigated by multivariate logistic regression. Results A total of 676 patients were enrolled in the study. Patients with extubation failure had a longer ICU length of stay and a higher mortality rate than patients without extubation failure. An age greater than 65 years, abnormal heart rate, respiratory rate exceeding 20 times/min, arterial pH lower than 7.35, pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FiO2) ratio lower than 300 mmHg, mean arterial pressure lower than 70 mmHg, duration of MV longer than 12 hours, and high quick Sequential Organ Failure Assessment (qSOFA) score were independent risk factors for extubation failure. Furthermore, we found that a respiratory rate greater than 20 times/min and a PaO2/fraction of Inspired Oxygen FiO2 ratio less than 300 mmHg were protective factors, while a mean arterial pressure lower than 70 mmHg, arterial pH lower than 7.35, and high qSOFA score were risk factors for deterioration on continued MV. Conclusions Since the duration of MV increases the risk of extubation failure, physicians should consider not only the risk of extubation failure but also the risk of deterioration with further MV.