Underwater endoscopic techniques have gained traction given their potential advantages. The aim of this multicenter randomized trial was to compare the effect of saline solution–immersion “underwater” peroral endoscopic myotomy (U-POEM) versus carbon dioxide insufflation during peroral endoscopic myotomy (CO ₂ -POEM) on postprocedural pain.

Consecutive patients with achalasia subtype I and II were randomized in a 1:1 ratio to U-POEM or CO ₂ -POEM during the study period between February 2025 and November 2025. Pain was assessed using the validated Numeric Pain Rating Scale (NPRS) on a scale of 0 (none) to 10 (most severe). The primary outcome was immediate postprocedural pain. Secondary outcomes included postprocedural pain at different times, requirement of analgesics, and clinical response (defined as a post-POEM Eckardt score < 3).

Thirty-six patients were randomized to U-POEM ( n = 18) and CO ₂ -POEM ( n = 18). Technical and clinical success rates were 100% in both groups with no immediate or delayed adverse events. There were no differences in dissection speed or procedural time between the 2 groups. The immediate post-POEM mean NPRS score was significantly lower in the U-POEM versus CO ₂ -POEM group (1.6 ± 1.6 vs 3.3 ± 2.6; 95% CI, 0.23-3.16; P = .02). Compared with CO ₂ -POEM, patients who underwent U-POEM reported less moderate-to-severe pain (16.7% vs 55.5%; 95% CI, 0.04-0.64; P = .04) and a lower number required opioids for postoperative pain management (5.5% vs 50%; 95% CI, 0.11-0.68; P = .007). Mean NPRS score remained lower in the U-POEM versus CO ₂ -POEM group at 72 hours after the procedure (1.13 ± 1.36 vs 2.26 ± 1.78; 95% CI, 0.06-2.20; P = .04).

U-POEM was safe, effective, and associated with lower postprocedural pain scores than CO ₂ -POEM (U-POEM trial: NCT06918730 ).