Remimazolam vs midazolam for sedation in upper gastrointestinal endoscopy: a systematic review and meta-analysis

Remimazolam, an ultra short-acting benzodiazepine with a rapid onset and predictable recovery, is increasingly recognized as an alternative to midazolam. We performed a systematic review and meta-analysis to assess the safety and efficacy outcomes of remimazolam compared with midazolam in diagnostic upper gastrointestinal endoscopy. A literature search was conducted in PubMed, Scopus, the Cochrane Library, and Web of Science from database inception to December 2025. Randomized controlled trials (RCTs) and non-randomized comparative studies were eligible. Forest plots were constructed using mean difference (MD) for continuous outcomes, and risk ratio (RR) for dichotomous outcomes using a random-effects model. heterogeneity was quantified using I². The study was registered in (PROSPERO) (ID: CRD420261287901). A total of four studies (three randomized controlled trials and one non-randomized study) were included. No significant differences were observed between remimazolam and midazolam in total procedure time (3 studies; MD: -5.74 min, 95% CI: [-17.76, 6.28], p = 0.3490), recovery time (2 studies; MD: -6.60 min, 95% CI: [-16.55, 3.34], p = 0.1928), total endoscopy time (2 studies; MD: -0.98 min, 95% CI: [-2.27, 0.31], p = 0.1367), and induction time (2 studies; MD: -0.21 min, 95% CI: [-1.52, 1.11], p = 0.7583). However, remimazolam showed a significantly shorter time from endoscopy to full alertness (2 studies; MD: -27.66 min, 95% CI: [-31.59, -23.72], p < 0.0001), and discharge time (2 studies; MD: -27.02 min, 95% CI: [-50.09, -3.95], p = 0.0217) compared with midazolam. Safety outcomes were comparable between remimazolam and midazolam. In conclusion, remimazolam may represent a safe and effective alternative to midazolam for upper gastrointestinal endoscopy, with faster cognitive recovery, as reflected by shorter time to full alertness and earlier discharge. Although a trend toward lower hypotension was observed with remimazolam, the difference did not reach statistical significance. These findings suggest that remimazolam may improve workflow efficiency and enhance patient experience in the endoscopy setting.