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Introduction: Spinal Anaesthesia (SA) is frequently associated with hypotension, which is due to sympathectomy causing vasodilation, leading to relative hypovolemia. This decrease in venous return to the heart causes a decrease in left ventricular filling pressure, leading to the activation of the Bezold-Jarisch Reflex (BJR), which causes bradycardia. This response is mediated by mechanoreceptors and chemoreceptors present on the heart walls. These chemoreceptors are mediated through serotonin (5-HT). Therefore, the activation of 5-HT3 receptors at sensory vagal nerve endings in the heart causes hypotension and bradycardia. Aim: To assess the efficacy of Palonosetron in attenuating spinal anaesthesia-induced hypotension and bradycardia. Materials and Methods: The trial was a parallel-design, randomised, double-blind controlled trial conducted over two years, from February 2021 to August 2022 in the Department of Anaesthesiology, Kalinga Institution of Medical Sciences (KIMS), Bhubaneswar, Odisha, India, among patients undergoing spinal anaesthesia for various surgeries. The patients were divided into two groups based on the type of medication received: Group A-Palonosetron group and Group B- the saline group. Computer-generated random number generator software was used for randomisation. At a 1:1 ratio, 150 patients were chosen (75 in each group). Baseline assessment of haemodynamic parameters was performed, followed by continuous monitoring. The drug was administered 10 minutes prior to spinal anaesthesia, and the haemodynamic parameters (Heart Rate [HR], Systolic Blood Pressure [SBP], Diastolic Blood Pressure [DBP], and Mean Arterial Pressure [MAP]) were monitored. Continuous variables are expressed as mean±Standard Deviation (SD). The Student's t-test was used to compare the difference between the two groups, and categorical variables are expressed as frequency and percentage, with comparisons done using the Chi-square test. A p-value of <0.05 was considered statistically significant. Results: The mean age of Group A and Group B was 40.88 and 42.14, respectively. Significant haemodynamic changes (hypotension) were observed following induction in Group B (28 [37.3%]) compared to Group A (9 [12%]). Consumption of vasopressors and intravenous (i.v.) fluids was significantly higher in Group B compared to Group A. The incidence of bradycardia in Group A and Group B was 15 (20%) and 18 (24%), respectively. Postoperative Nausea and Vomiting (PONV) in Group A and Group B were 3 (4%) and 8 (10.7%), respectively. Conclusion: Based on the present study, the prophylactic administration of 0.075 mg Palonosetron 10 minutes before subarachnoid block is effective in attenuating the incidence of spinal anaesthesia-induced hypotension and bradycardia. There is also decreased consumption of vasopressors and a lower incidence of PONV. [ABSTRACT FROM AUTHOR]