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Background: The frequency of shivering regarding regional anesthesia is 55%. Newer effective and tolerable options for postspinal anesthesia shivering (PSAS) prophylaxis are necessary to improve patients' quality of care. This research assessed the impact of preemptive mirtazapine versus preemptive dexamethasone to decrease frequency and severity of PSAS in gynecological procedures., Methods: 300 patients booked for gynecological procedures under spinal anesthesia (SA) were randomly apportioned into three groups (100 each) to get one preemptive dose of 30 mg mirtazapine tablet (M group), 8 mg dexamethasone diluted in 100 ml of saline infusion (D group) or placebo (C group) two hours before surgery. Incidence of clinically significant PSAS was the primary outcome. Core temperature, shivering score, hemodynamics changes, adverse events, and patient satisfaction score were documented as secondary outcomes., Results: Compared with C group, mirtazapine and dexamethasone decreased incidence of clinically significant shivering (74% vs. 16% and 31%, respectively; P < 0.001). M and D groups had less hypotensive episodes during 5-25 min after intrathecal injection ( P < 0.001). 90 min after SA, tympanic temperatures were lower than baseline values in the three groups ( P < 0.001). Pruritus, nausea, and vomiting were more often in C group ( P < 0.001), whereas sedation was more frequent in M group ( P < 0.001). C group had the lowest satisfaction scores ( P < 0.001)., Conclusion: Prophylactic administration of mirtazapine or dexamethasone attenuated shivering with minimal hazards in patients scheduled for gynecological surgeries under spinal anesthesia with priority to mirtazapine. The trial is registered with NCT03675555., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Ibrahim M. Esmat et al.)