Objective:　Postoperative　pain　is　a　common　yet　often　underestimated　complication　following　esophageal　endoscopic　submucosal　dissection　(ESD),　with　limited　strategies　for　effective　management.　This　prospective,　double-blind,　randomized　controlled　trial　assessed　the　effects　of　adding　dexmedetomidine　(DEX)　to　the　anesthesia　regimen　on　postoperative　pain　and　early　recovery　in　patients　undergoing　esophageal　ESD.　Methods:　In　total,　60　patients　scheduled　for　elective　esophageal　ESD　under　general　anesthesia　were　randomly　assigned　to　the　DEX　or　control　group.　The　DEX　group　received　an　intravenous　loading　dose　of　DEX　at　1 μg/kg　for　10 min,　followed　by　a　continuous　intravenous　infusion　of　0.6 µg/kg/h,　which　was　stopped　30 min　before　the　end　of　the　procedure.　The　control　group　received　normal　saline　as　a　placebo.　The　study＇s　primary　outcome　was　the　incidence　of　moderate-to-severe　postoperative　pain.　Secondary　outcomes　included　postoperative　pain　scores,　hemodynamic　parameters,　the　occurrence　of　postoperative　nausea　and　vomiting　(PONV),　patient　satisfaction,　and　lengths　of　stay　in　the　post-anesthesia　care　unit　(PACU)　and　hospital.　Results:　The　incidence　of　moderate-to-severe　postoperative　pain　in　the　DEX　group　was　significantly　lower　than　that　in　the　control　group　(absolute　difference:　-33.4%;　OR:　0.250;　95%　CI:　0.085-0.731,　P　=　0.01).　Pain　scores　at　1 h　postoperatively　(0.5[2.0]　vs　3.0[1.3],　P　=　0.003)　were　significantly　lower　in　the　DEX　group.　Additionally,　morphine　dosage　in　the　PACU　(0[0]　vs　1.0[2.0]　P　=　0.004)　was　significantly　reduced　in　the　DEX　group　compared　with　the　control　group.　In　the　DEX　group,　the　incidence　and　severity　of　PONV　were　significantly　decreased　and　the　length　of　PACU　stay　was　shorter　than　in　the　control　group　(P　＜　0.01).　However,　the　rates　of　intraoperative　hypotension,　tachycardia,　and　bradycardia　were　similar　between　the　two　groups.　Patient　satisfaction　and　length　of　hospital　stay　were　also　comparable.　Conclusion:　Adding　DEX　to　the　anesthesia　regimen　for　esophageal　ESD　significantly　attenuates　postoperative　pain　and　improves　early　recovery　outcomes.　©　2024　Luo　et　al.