Background: Tracheal intubation is a noxious stimulus that tends to provoke a marked sympathetic response which is potentially deleterious in some patients. Various methods have been used to minimize and attenuate these potentially harmful responses. Aim of the study: The present study compared the efficacy and safety of two different doses (150 mg and 300 mg) of oral pregabalin premedication on attenuation of the hemodynamic pressor response to airway instrumentation, perioperative hemodynamic stability, preoperative sedation, and postoperative pain reduction. Patients and methods: This prospective, observational study consisted of 60 adult patients scheduled for laparoscopic cholecystectomy. The patients were randomized into three groups of 20 patients each. Group I (P0) received an oral placebo, group II (P150) received 150 mg of oral pregabalin and group III (P300) received 300 mg of oral pregabalin 1 h prior to induction. All patients were assessed for pre-operative sedation, perioperative hemodynamic changes, Post-operative pain and analgesic consumption. Results: Regarding the efficacy of the preoperative administration of oral pregabalin, a dose dependent attenuation in the increased in heart rate, systolic, and diastolic blood pressure, and mean arterial blood pressure resulting from laryngoscopy and intubation was observed (300 mg > 150 mg), along with a subsequent decrease in intraoperative fentanyl supplementation. On anxiolysis, patients were more comfortable and asleep in the pregabalin groups as compared with the control group, in which more patients were awake and agitated. Post-operative pain and analgesic consumption were effectively reduced by (150 mg and 300 mg) pregabalin in a dose-dependent manner. Postoperative nausea and vomiting were significantly lower with the administration of pregabalin compared with the placebo group (P < 0.008). Additionally, pregabalin increased the incidence of dizziness and visual disturbances in a dose-dependent manner. Conclusion: Oral pregabalin premedication adequately sedated patients and attenuated the hemodynamic pressor response to airway instrumentation in a dose-dependent manner. Premedicated patients were haemodynamically stable perioperatively without recovery time prolongation or side effects, except dizziness with 300 mg of oral pregabalin. Additionally, oral pregabalin reduced postoperative pain and analgesic consumption in a dose-dependent manner.