Objective  To investigate the efficacy and safety of flexible ureteroscope(FURL) and minimally invasive percutaneous nephrolithotomy(MPCNL) in the treatment of 2～3 cm renal calculi. Methods  From January 2017 to January 2020, 98 patients with renal calculi in our hospital were selected and divided into two groups according to different treatment methods, with 49 cases in each group. The control group was treated with MPCNL, and the study group was treated with FURL. The operation conditions, stone clearance rate, pain and comfort score and quality of life of the two groups were observed.Results  The operation time, intraoperative blood loss, postoperative ambulation time, and hospitalization time in the study group were better than those in the control group, and the differences were statistically significant (all P<0.001). The stone clearance rate of the study group was higher than that of the control group at 3 days after operation, and the difference was statistically significant (P<0.05), but there was no statistically significant difference in the stone clearance rate between the two groups at 1 week and 1 month after operation (all P>0.05). The pain scores of the study group at 5 h and 48 h after surgery were lower than those of the control group, and the comfort scores were higher than those of the control group, and the differences were statistically significant (P<0.05). There was no statistically significant difference in the quality of life between the two groups before treatment (P>0.05). The quality of life of the study group was higher than that of the control group at discharge, and the differences were statistically significant (P<0.05).Conclusions  FURL and MPCNL are good for 2～3 cm renal calculi, but FURL can shorten the operation time, shorten the hospitalization time, improve the postoperative quality of life, and improve the pain comfort of patients.