Abstract: Objective: To compare the effects of remimazolam and propofol on postoperative fatigue syndrome (POFS) in elderly patients undergoing laparoscopic cholecystectomy (LC). Methods: A prospective randomized controlled trial was conducted,enrolling 84 elderly patients scheduled for elective LC.Participants were randomly divided into the remimazolam group (group R,n=42) and the propofol group (group P,n=42).Postoperative day 1 (D1) and day 2 (D2) Christensen fatigue scores,POFS incidence,inflammatory stress markers (IL-6,TNF-α,cortisol),hemodynamic changes,anesthetic consumption,recovery quality,and adverse reactions were recorded. Results: On D1,the Christensen fatigue score in group R was significantly lower than that in group P (P<0.01),and the POFS incidence was also lower (P<0.05).On D2,the fatigue score in group R further decreased (P<0.01),but no statistically significant difference in POFS incidence was observed between the two groups (P>0.05).Inflammatory stress markers showed that Group R had lower levels of IL-6,TNF-α,and cortisol on both D1 and D2 compared to group P (P<0.01).Group R exhibited more stable hemodynamics and a lower incidence of hypotension (P<0.05).No significant difference in recovery time was noted between the two groups (P>0.05),but group R demonstrated superior post-awakening agitation scores (Riker-SAS) and analgesic requirements compared to group P (P<0.05).Additionally,group R had reduced consumption of opioids and muscle relaxants (P<0.05). Conclusions: Remimazolam significantly reduces postoperative fatigue scores and POFS incidence in elderly LC patients,potentially due to its ability to inhibit inflammatory stress responses,stabilize hemodynamics,and decrease anesthetic consumption.Compared to propofol,remimazolam offers greater advantages in perioperative management for elderly LC patients.