Background <p>Remimazolam, a novel ultra-short-acting benzodiazepine, shows promise for sedation in endoscopic procedures. However, its cardiovascular effects during painless gastroscopy remain unclear. This study compared the effects of remimazolam and propofol on hemodynamic stability in patients undergoing painless gastroscopy using continuous non-invasive arterial pressure (CNAP) monitoring.</p> Methods <p>A total of 300 patients scheduled for sedation during upper gastrointestinal endoscopy were randomly assigned to either the remimazolam group (Group R, <i>n</i> = 150) or the propofol group (Group P, <i>n</i> = 150). Group R received remimazolam tosilate (0.2&#xa0;mg/kg), while Group P received propofol (2&#xa0;mg/kg). Primary outcomes were mean arterial pressure (MAP) and cardiac output (CO), recorded at two time points: the start (T1) and completion (T2) of the examination. Secondary outcomes included adverse events such as injection-related pain, hypotension, hypoxemia, respiratory depression, and bradycardia.</p> Results <p>At both assessment points, MAP was significantly higher in Group R than in Group P (82.5 vs. 75.0 mmHg at T1, <i>p</i> &lt; 0.001; 82.0 vs. 77.0 mmHg at T2, <i>p</i> = 0.002). Additionally, CO was significantly higher in Group R (5.7 vs. 5.4&#xa0;L/min, <i>p</i> = 0.017). The incidence of adverse events was greater in Group P compared to Group R, including injection pain (25.3% vs. 6.7%), hypotension (24.7% vs. 5.3%), hypoxia (5.3% vs. 0%), and bradycardia (14.7% vs. 0%).</p> Conclusion <p>Both remimazolam and propofol provide effective sedation for painless gastroscopy. However, remimazolam offers superior hemodynamic stability and significantly fewer adverse events.</p> Trial registration <p>The study was subsequently documented in the Chinese Clinical Trial Registry (identifier: ChiCTR2300068901; registration date: March 1, 2023).</p>