Background: Peri-extubation cough is an undesirable event during extubation, prevention of which has been studied with multiple drugs, amongst which intravenous dexmedetomidine has emerged as one of the favourable drugs. Intratracheal route is attractive because of its ease of administration, provided it avoids the hypotension and bradycardia that occurs during intravenous bolus administration. There is a paucity of data exploring the utility, doses, and adverse effect of intratracheal dexmedetomidine. Methods: After obtaining ethical committee approval, 60 eligible, consenting adult patients undergoing surgery under general anesthesia in a tertiary teaching hospital were recruited and randomised into three groups—DEX0.3, DEX0.5, and NS. The plan of general anesthesia was standardized. Half an hour prior to extubation, study drug was instilled intratracheally—dexmedetomidine 0.3 mic/kg, 0.5 mic/kg, and NS in groups DEX0.3, DEX0.5, and NS, respectively. 4-point cough score was used to assess extubation response. Hemodynamic response and time to Ramsay sedation score 3 was also recorded. Results: Majority of patients in DEX0.3 (60%) and DEX0.5 (85%) group had no cough (cough score 0), while majority of the patients in the NS group (70%) had either mild or moderate cough (cough score 1, 2). Kruskal Wallis test followed by post-hoc pairwise comparison showed statistically significant difference in 4-point cough score between GroupDEX0.3 and GroupNS ( P < 0.001) and between GroupDEX0.5 and GroupNS ( P = 0.038). DEX0.5 group, compared to DEX0.3 group, had significantly higher time from reversal to extubation ( P < 0.001) and time to achieve Ramsay sedation score of 3 ( P < 0.001). Conclusion: We conclude that both 0.3 mic/kg and 0.5 mic/kg of dexmedetomidine when given intratracheally are effective in preventing peri-extubation cough. Further, 0.3 mic/kg dexmedetomidine showed a better recovery profile compared to 0.5 mic/kg dexmedetomidine when administered intratracheally.