Background: Opioid-free anesthesia (OFA) is gaining prominence, particularly in neurosurgery, due to its potential to minimize opioid-related complications such as postoperative nausea and vomiting (PONV) and shivering. This Prospective observational study aims to compare the efficacy of a standard drug dose mixture comprising intravenous magnesium sulphate, lignocaine, paracetamol, and tramadol with fentanyl in attenuating the hemodynamic stress response during laryngoscopy and tracheal intubation. Methods: Sixty neurosurgical patients, aged 18 to 60 years, undergoing cervical or lumbar discectomies under general anesthesia in our institute were divided into two groups. One group received the standard drug dose mixture, and the other received fentanyl. Hemodynamic parameters, including pulse rate, blood pressure, oxygen saturation (SpO2), and electrocardiogram (ECG) changes, were recorded at baseline, during intubation, and at one- minute intervals for five minutes post-intubation. Results: Both groups demonstrated stable hemodynamics with no significant differences in pulse rate or blood pressure. No ECG abnormalities were observed, and SpO2 remained above 96% in all patients. Additionally, the standard drug dose mixture group showed a reduced incidence of PONV and shivering compared to the fentanyl group. Conclusion: The standard drug dose mixture provides a safe and effective alternative to fentanyl for attenuating the hemodynamic stress response during laryngoscopy and tracheal intubation, with fewer side effects. Further randomized controlled trials are recommended to confirm these findings and explore the benefits of opioid-free anesthesia in various surgical procedures.