Background: The most common complications after tracheal intubation during general anesthesia are sore throat, hoarseness, and laryngospasm which can cause severe discomfort to patients. Several methods have been suggested to prevent these complications. In this study, the effects of intracuff dexamethasone, lidocaine, and normal saline in reducing post-extubation reactions were compared. Methods: This double-blind clinical trial was performed on 240 men of ASA (American Society of Anesthesiologists) class I or II who underwent general anesthesia for elective procedures in KVG medical college and hospital, Sullia during 2017-18. Depending on the kind of drug used to fill the endotracheal tube (ETT) cuff, patients were randomly allocated into normal saline, lidocaine, and dexamethasone groups. Post-extubation reactions were then evaluated in all groups. Results: The groups were demographically comparable. There were no significant differences between the three groups regarding post-extubation sore throat, hoarseness, or laryngospasm (p > 0.05). However, a significant difference in cough existed between the three groups (p = 0.02). No significant differences were detected between the three groups regarding hemodynamic variables. Conclusion: The three drugs were not significantly different in attenuating post-extubation reactions such as hoarseness, sore throat, and laryngospasm. However, lidocaine was more effective on cough incidence while dexamethasone had better efficacy in reducing cough severity. ETT tolerance was more in the lidocaine group than the other two groups.