Objective To compare the safety and efficacy of SpyGlass DS system laser lithotripsy and conventional fractional treatment under endoscopic retrograde cholangiopancreatography(ERCP)in treatment of large calculus of common bile duct.Method 38 patients with large calculus of common bile duct(>2 cm)during ERCP from November 2021 to October 2023 were selected and divided into experimental group(n=18)and control group(n=20).The experimental group was treated with SpyGlass DS system combined with laser lithotripsy.The patients in the control group were treated with split treatment(the first biliary stent was placed,and the calculus of common bile duct were removed under conventional ERCP again 3 months later).The success rate of stone clearance and the incidence of complications after ERCP were compared between the two groups.Magnetic resonance cholangiopancreatography(MRCP)was performed 3 months after surgery to determine whether there were residual calculus of common bile duct.Results The surgical time of the experimental group was longer than that of the control group,and the difference was statistically significant(P<0.05).There was no significant difference in the stone clearance rate and the incidence of short-term complications between the two groups(P>0.05).The incidence of long-term complications in the experimental group was lower than that in the control group,but the difference was not statistically significant(P=0.090).Conclusion SpyGlass DS guided laser lithotripsy is effective and safe for the treatment of large calculus of common bile duct,with a low recurrence rate.