Introduction: Urinary stone disease is the third most common affliction of the urinary tract that has been associated with an increasing incidence. Over decades, great advances have been made in the minimally invasive treatment of urinary stones. Recently, transurethral lithotripsy (TUL) by holmium laser was introduced as a possible therapeutic option. This study evaluated the effect of propofol on the success rate of TUL by holmium laser.Methods: A double-blind randomized controlled trial was conducted on 180 patients to investigate the effect of propofol on the success and complication rate of TUL by holmium laser. The enrolled patients were divided into two groups: the first group received sodium thiopental (n = 89) while the second group received propofol (n = 91). The two groups were compared in terms of the fluctuations of systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), operation time, future stone-free rate (SFR), stone migration, post-operative fever, and ureteral complications such as perforation and mucosal damage. Other developed complications were also recorded. After data gathering, statistical analysis was performed with SPSS version 21.Results: the patients’ data such as age, sex, stone diameter, stone laterality, duration of stone impaction, primary SBP, DBP and HR were not significantly different between the two groups (P > 0.05). TUL and anesthesia duration, first-minute and fifth-minute SBP and DBP, and also changes of HR were significantly lower in the propofol group compared with the sodium thiopental group (P < 0.001). Moreover, SFR of TUL was more evident in the propofol group. Ureteral mucosal damage was significantly less in the propofol group.Conclusion: Propofol was associated with a higher reduction in SBP and DBP, decreased duration of TUL, fewer fluctuations in HR, and an increased success rate of stone removal by TUL with holmium laser