Objective: This study aimed to assess the effect of intraoperative dexmedetomidine (DEX) on pain outcomes after craniotomy.Methods: Eighty patients scheduled for supratentorial craniotony were randomly allocated into two groups, to receive 0.5 μ g/kg/h DEX infusion or placebo intraoperatively.Tramadol was administered to achieve VAS≤4 in after surgery.Pain scores, tramadol consumption, sedation and PONV scores, and adverse events were recorded.Results: Seventy-six patients were included.DEX reduced pain scores (30min, P=0.041, and 2h, P=0.021) and tramadol consumption (0-2h, P=0.043;0-6h, P=0.006;0-12h, P=0.023;and 0-24h, P=0.040).It also reduced PONV scores at 20, 60, 90, 120, and 240 min (P=0.038, 0.022, 0.018, 0.037, 0.016, respectively).The dexmedetomidine group exhibited fewer PONV events (P=0.005).Conclusion: Intraoperative DEX infusion was effective for reducing pain and analgesic consumption after craniotomy.Additionally, it may help to reduce PONV.