Objective: To analyze the influence of operator's experience on the quality and success rate of root canal treatment with new nickel-titanium instruments, providing support for improving the success rate of root canal treatment with new nickel-titanium instruments in clinic. Methods: Cases of root canal treatment and non-surgical root canal retreatment with 6-12 months recall performed by residents (resident group) with experience of 1-3 years and endodontic specialists (specialist group) with experience of 5-7 years were collected from the electronic medical system of the Department of Endodontics, School of Stomatology, Capital Medical University, from September 2020 to August 2021. All cases were prepared by engine-driven glide path files and controlled memory nickel-titanium finishing files. Chi-square test and logistic regression were used to analyze the differences and influencing factors of complications, filling quality and success rate of root canal treatment between the two groups. Results: A total of 277 cases performed by 24 residents and 3 specialists were included, 169 in the resident group and 108 in the specialist group. The clinical incidence of flare-ups was significantly higher in the resident group [3.6% (6/169)] than in the specialist group [0(0/108)] (P=0.048). There were no significant differences in ledges, root canal transportations, perforations, or instrument separations between the two groups (P>0.05). The prevalence of satisfactory fillings was 62.7% (106/169) in the resident group, which was significantly lower than that in the specialist group [86.1% (93/108)] (P<0.05). The success rate of root canal treatment was 91.7% (155/169) and 94.4% (102/108) in the resident group and the specialist group, respectively, with no significant differences (χ2=0.73,P=0.392). Multivariate analysis showed that the success rate of root canal treatment was related to complications and quality of root fillings (P<0.05). Conclusions: Higher success rate of root canal treatment could be achieved by residents and endodontic specialists with engine-driven glide path files and controlled memory nickel-titanium files.