Introduction: Transsphenoidal resection of pituitary tumours presents challenges for an anaesthesiologist due to haemodynamic fluctuations caused by intense nociceptive stimuli during different surgical stages. This relatively short procedure requires a smooth and rapid emergence for spontaneous airway control and assessment of surgical outcomes. Therefore, the chosen anaesthetic agent should provide effective haemodynamic control and facilitate rapid recovery. Alpha-2 agonists such as dexmedetomidine and clonidine are known to centrally decrease noradrenaline release, thus reducing sympathetic outflow. This could be particularly beneficial in minimising haemodynamic fluctuations during such surgeries. Aim: To compare the effects of preoperative clonidine and perioperative dexmedetomidine in attenuating haemodynamic responses and blood loss in patients undergoing elective Transnasal Transsphenoidal resection (TNTS) of pituitary tumours. Materials and Methods: A randomised, double-blinded study was conducted in the Department of Neuroanesthesiology at Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India, over a period of one year, from February 2022 to January 2023. Sixty patients of either sex, aged 18-65 years with ASA I or II, scheduled for elective TNTS pituitary surgery, were enrolled and divided into group A and group B. Group A received clonidine tablets (3 mcg/kg) 180 minutes prior to surgery, while group B received intravenous (i.v.) infusion of dexmedetomidine (1 mcg/kg/min) over 10 minutes before induction, followed by 0.5-0.7 mcg/kg/hr. Group A received a placebo of 0.9% Normal Saline (NS) (50 mL). Heart Rate (HR), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Mean Arterial Pressure (MAP) were recorded at baseline, intubation, nasal pack insertion, endoscope insertion, and at various time intervals. Data obtained were analysed using unpaired sample t-test for independent groups, and Chi-square test was used for categorical data. A probability value of 0.05 was considered significant for both statistical tests. Results: The mean age of participants was 42±11 years for group A and 43±12 years for group B, with a male: female ratio of 66.6% to 33.3% in group A and 70% to 30% in group B, respectively. The mean Body Mass Index (BMI) was 26.4±3.2 in group A and 25.2±1.7 in group B. HR, SBP, and MAP decreased at various stages in group B compared to group A, and these differences were statistically significant (p-value <0.05). The study also found that the total consumption of propofol was significantly less in group B (220±38) compared to group A (282±140). Similarly, total fentanyl consumption was significantly lower in group B (5.83±1.60) than in group A (16.6±23.9). Although not statistically significant, total blood loss was also lower in group B (115±63) compared to group A (156±108). Conclusion: Intraoperative infusion of i.v. dexmedetomidine provides a reasonable choice compared to orally administered clonidine for transsphenoidal pituitary tumour resection, considering its favorable effects on haemodynamic stability and anaesthetic requirements.