ABSTRACT Background: Laryngoscopy and endotracheal intubation are an integral part of an anaesthesiologist’s contribution to patient care and are regarded as one of the core skills of anesthesiologist. A number of pharmacological measures have been used to attenuate the hemodynamic stress response associated with larngoscopy and intubation. Aim: To evaluate the effect of oral Clonidine 300 mcg vs oral Pregabalin 75 mg premedication in attenuating the hemodynamic response following laryngoscopy. Methods: The study was designed as a hospitalbased prospective observational trial involving 120 patients of ASA physical status I ofeither sex scheduled to undergo elective general surgical procedures under general anaesthesia. The patients were randomly allocated to three equal groups of 40 each bymeans of a computer-generated table of random numbers. The Heart Rate, Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP),Mean Arterial Pressure values, and arrhythmias (if any) were recorded. Statistical testing was conducted with the statistical package for the social science system (SPSS) version 17.0. Continuous variables were presented as mean±SD ormedian (IQR) for non-normally distributed data. Categorical variables were expressed as frequencies and percentages. Results: The heart rate increased by 27.7% 1 min after direct laryngoscopy and endotracheal intubation compared to baseline value in the placebo group (p<0.01). Asimilar increase in pregabalin group was 29.9% and in clonidine group was 12.7%. The mean arterial pressure increased by 28.5% in placebo group while it increased by 26.6% in pregabalin group and only by 11.17% in clonidine group compared to baseline values during laryngoscopy and intubation. Attenuation of mean arterial pressure is significant in clonidine group as compared to both pregabalin and placebo groups (p<0.01). With regard to arrhythmia, which was our secondary objective, it was observed that none of the patients who participated in our study developed arrhythmias, either at induction or anytime later during the surgeries. Conclusion: Oral clonidine (300µg) given 120 min before induction was effective in attenuating hemodynamic stress response to laryngoscopy and endotracheal intubation. There was no statistically significant difference between placebo and pregabalin groups.