- To evaluate whether inhaled nitrous oxide with oxygen (N2O/O2) is associated with less pain compared to oral sedation for pain management during in-office hysteroscopic sterilization.This double blinded randomized controlled trial enrolled women undergoing in-office hysteroscopic sterilization. All participants received pre-procedure intramuscular ketorolac and a standardized paracervical block. The intervention group also received N2O/O2 via a nasal mask titrated to a maximum 70%:30% mixture by a nurse during the procedure and placebo pills pre-procedure and the active control group received inhaled O2 during the procedure and 5/325 mg hydrocodone/acetaminophen and 1 mg lorazepam pre-procedure. The primary outcome was maximum procedure pain on a 100 mm Visual Analog Scale (VAS with anchors at 0=no pain and 100=worst imaginable pain) assessed 3-5 min post procedure. Thirty women per treatment arm were required to detect a clinically significant pain difference of 20 mm.Seventy-two women, 36 per study arm, were randomized. Mean age of participants was 34.1±5.7 years and mean BMI was 30.1±6.6kg/m(2). Mean maximum procedure pain scores were 22.8±27.6 mm and 54.5±32.7 mm for intervention and control groups, respectively (p<.001). Most study participants (97%) stated N2O/O2 should be offered for gynecologic office procedures and 86% would pay for it if not a covered benefit.N2O/O2 decreased pain with in-office hysteroscopic sterilization compared to oral sedation and is an effective pain management option for this procedure.Given its safety and favorable side effect profile, N2O/O2 can be used for pain management for in-office hysteroscopic sterilization and adds a safe, easily administered option to currently available strategies.Copyright © 2016 Elsevier Inc. All rights reserved.