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Background: Re-intubation of neurosurgical patients after a successful tracheal extubation in the operating room is not uncommon. However, no prospective study has ever addressed this concern. This study was aimed at analyzing various risk factors of re-intubation and its effect on patient outcome. Methods: Patients aged between 18-60 yrs and of ASA physical status I and II undergoing elective craniotomies over a period of two yrs were included. A standard anesthetic technique using propofol, fentanyl, rocuronium, and isoflurane/sevoflurane was followed, in all these patients. ′Re-intubation′ was defined as the necessity of tracheal intubation within 72 hrs of a planned extubation. Data were collected and analyzed employing standard statistical methods. Results: One thousand eight hundred and fifty patients underwent elective craniotomy, of which 920 were included in this study. A total of 45 (4.9%) patients required re-intubation. Mean anesthesia duration and time of re-intubation were 6.3±1.8 and 24.6±21.9 hrs, respectively. The causes of re-intubation were neurological deterioration (55.6%), respiratory distress (22.2%), unmanageable respiratory secretion (13.3%), and seizures (8.9%). The most common post-operative radiological (CT scan) finding was residual tumor and edema (68.9%). Seventy-three percent of the re-intubated patients had satisfactory post-operative cough-reflex. The ICU and hospital stay, and Glasgow outcome scale at discharge were not significantly affected by different causes of re-intubation. Conclusion: Neurological deterioration is the most common cause of re-intubation following elective craniotomies owing to residual tumor and surrounding edema. A satisfactory cough reflex may not prevent subsequent re-intubation in post-craniotomy patients.