Abstract:Objective To evaluate the efficacy and safety of SpyGlass, in addition, to compare the efficacy of first/second-generation SpyGlass, electrohydraulic and laser lithotripsy in treating difficult bile duct stones.Methods Several Chinese and English databases were searched up to February 2021. The methodological quality of studies was evaluated by Newcastle-Ottawa Scale (NOS) and JADAD scale, and random-effects models were used to calculate the pooled estimates. Important outcomes were complete stone clearance rate, single-session stone clearance rate, stone removal times and adverse events rate.Results 37 studies met the inclusion criteria, involving 3 728 patients. The complete stone clearance rate was 0.947 (95%CI: 0.920 ~ 0.970), the single-session stone clearance rate was 0.747 (95%CI: 0.682 ~ 0.807), the stone removal times was 1.10 (95%CI: 1.080 ~ 1.120), and the adverse events rate was 0.065 (95%CI: 0.046 ~ 0.087); The second-generation SpyGlass is superior to the first-generation SpyGlass in the complete/single-session stone clearance rate and the stone removal times (97.3% vs 92.2%, 80.3% vs 67.8%, 1.03 vs 1.27); Electrohydraulic lithotripsy is superior to laser lithotripsy in the complete/single-session stone clearance rate, the stone removal times and the adverse events rate (97.8% vs 91.0%, 80.4% vs 70.1%, 1.06 vs 1.19, 6.5% vs 7.8%).Conclusion SpyGlass is a safe and effective treatment for difficult bile duct stones when conventional stone removal has failed, the second-generation SpyGlass combined with laser lithotripsy may get a better effect.