Context: Endotracheal intubation and laryngoscopy are basic and fundamental tools of anaesthesiologists to take care of the airway. It is important to find an effective means of attenuating sympathetic response to laryngoscopy and intubation. Aims: Our aim was to compare and assess the efficacy of i.v esmolol and fentanyl before laryngoscopy and tracheal intubation and to observe the variations in sympathetic response to laryngoscopy and intubation. Methods and Materials: This study was a prospective randomized doubleblind study on patients undergoing ENT, orthopaedics, gynaecological, general surgical, neurological and laparoscopic procedures. A clinical comparative study of attenuation of the sympathetic response to laryngoscopy and intubation was done in 60 patients of American Society of Anesthesiologist (ASA) grade I or II, age between 20 to 50 years of both the sexes and Mallampati airway assessment of grade I, posted for elective surgeries selected randomly. In study group I (n=30) patients receive 2 mg/kg esmolol IV, 3 minutes before laryngoscopy and intubation. In study group II (n=30) patients in this group receive 2 µg/kg of fentanyl IV, 5 minutes before laryngoscopy and intubation. Statistical analysis used: The statistical analysis was done by STATA 11.2 (College Station TX USA). Students independent sample t-test and Chi-square test were used. p < 0.05 considered as statistically significance. Results: Maximum rise in systolic blood pressure was observed at the post-intubation first minute, i.e., 133.73 ± 10.36 and 144.43 ± 10.92 in the Group I and II from the baseline, respectively but maximum rise of heart rate (103.43 ± 7.50) was during the first minute in group I but maximum rise of heart rate (87.83 ± 5.45) was in group I. The diastolic blood pressure and mean arterial pressure changes was significant between fentanyl and esmolol groups at 1 and 3 minute and post-induction, 1 and 5 minute respectively. Group I showed better control of heart rate during laryngoscopy and intubation at the first, 3 and 10 min after intubation compared to other groups (p < 0.05). Conclusions: Esmolol is more effective than fentanyl in attenuation of the sympathetic response to laryngoscopy and intubation.