Background <p>To assess the safety of ciprofol for painless gastroenteroscopy in obese patients by comparing the effects of ciprofol-remifentanil and propofol-remifentanil on hemodynamic parameters, respiratory function, and other adverse reactions.</p> Methods <p>A total of 70 obese patients who underwent painless gastrointestinal endoscopy at Longyan First Hospital of Fujian Medical University (Longyan, China) from September 2023 to February 2024 were enrolled. They were randomly assigned into the propofol group (Group A) and the ciprofol group (Group B) by a random number table. Group A received propofol combined with remifentanil anesthesia during the endoscopy, while Group B received ciprofol combined with remifentanil anesthesia. The systolic blood pressure, diastolic blood pressure, heart rate, and peripheral capillary oxygen saturation (SpO₂) levels were compared between the two groups at pre-anesthesia (T0), 1-min post-anesthesia (T1), 3-min (T2), 6-min (T3), 12-min (T4), and 5-min post-recovery (T5). Arrhythmias, hypotension, tachycardia, bradycardia, and the use of vasoactive drugs were documented. Additionally, the incidence and average severity of hypoxemia, the average duration of hypoxemia, and the average minimum SpO₂ level were recorded. The occurrence rates of jaw thrust, mask ventilation, nasopharyngeal airway insertion, tracheal intubation, and other adverse reactions were recorded.</p> Results <p>Compared with Group A, Group B exhibited significantly higher blood pressure levels at T1 and T2, as well as higher SpO₂ levels at T1, T2, and T3 (<i>P</i> &lt; 0.05). The incidence of hypotension was lower in Group B (<i>P</i> &lt; 0.05), and no significant differences were identified in arrhythmias, tachycardia, bradycardia, or the use of vasoactive drugs between the two groups. Group B also demonstrated a lower incidence of hypoxemia, reduced average severity, shorter duration, and a higher minimum SpO₂ level compared with Group A (<i>P</i> &lt; 0.05). Additionally, Group B required fewer jaw thrust interventions (<i>P</i> &lt; 0.05) and had a significantly lower incidence of injection pain (<i>P</i> &lt; 0.05). No significant differences were found in the incidence of other adverse reactions between the two groups.</p> Conclusion <p>The ciprofol-remifentanil combination used in painless gastroenteroscopy in obese patients resulted in more stable hemodynamics, significantly reduced respiratory depression, and less injection pain.</p> Trial registration <p>The trial was registered in the China Clinical Trials Registry (Registration No. ChiCTR2300075619, Date of registration: 11/09/2023).</p>