https://www.selleckchem.com/products/genipin.html AIM To identify the highest-ranked pharmacological and nonpharmacological interventions for pain relief during outpatient hysteroscopy. METHODS We conducted an online bibliographic search in different databases from inception till July 2019. We included randomized controlled trials assessing effect of pharmacological and nonpharmacological interventions on pain relief during outpatient hysteroscopy. Our main outcomes were pain scores at different endpoints of the procedure. We applied this network meta-analysis based on the frequentist approach using statistical package 'netmeta' (version 1.0-1) in R. RESULTS The review included 39 randomized controlled trials (Women n = 3964). Misoprostol plus intracervical block anesthesia (mean difference [MD] = -3.32, 95% confidence interval [CI] [-6.06, -0.59]), misoprostol (MD = -1.92, 95% CI [-3.04, -0.81]) and IV analgesia (MD = -2.01, 95% CI [-3.27, -0.25]) were effective in reducing pain during the procedure compared to placebo. Ranking probability showed that misoprostol plus intracervical block anesthesia was the highest ranked pharmacological treatment for pain relief during the procedure (P score = 0.92) followed by misoprostol alone (P score = 0.78), and IV analgesia (P score = 0.76). Regarding nonpharmacological treatments, transcutaneous electrical nerve stimulation (TENS) showed a significant pain reduction compared to placebo (MD = -1.80, 95% CI [-3.31, -0.29]). TENS ranked as the best nonpharmacological treatment (P score = 0.80) followed by CO2 distention (P score = 0.65) and bladder distention (P score = 0.60). CONCLUSION Combination of misoprostol plus local anesthesia appears to be the most effective pharmacological approach for pain reduction during and after outpatient hysteroscopy. Nonpharmacological approaches as TENS and bladder distention showed considerable efficacy but should be further investigated. © 2020 Japan Society of Obstetrics and Gynecology.AI