Objective To investigate the curative effect and safety of microinvasive percutaneous nephrolithotomy (MPCNL) and ureteroscope lithotripsy (URSL) in treatment of children′s (≤6 years old) middle and upper segment ureteral calculi. Methods Eighty children (≤6 years old) with middle and upper segment ureteral calculi were selected, and they were divided into observation group and control group according to random number table method with 40 cases each. The children of observation group were treated with MPCNL, and the children of control group were treated with URSL. The operation time, hospitalization time, calculi clearance rate of the first phase, decline situation of the postoperative hemoglobin and hematocrit and complication were compared between 2 groups. Results The operation time and hospitalization time in observation group were significantly shorter than those in control group:(45.43 ± 9.76) min vs. (68.32 ± 11.28) min and (8.12 ± 1.03) d vs. (13.45 ± 2.34) d, the calculi clearance rate of the first phase was significantly higher than that in control group: 100.0% (40/40) vs. 62.5%(25/40), the incidence of complication was significantly lower than that in control group:20.0%(8/40) vs. 60.0% (24/40), and there were statistical differences (P<0.05). There were no statistical differences in the decline situation of the postoperative hemoglobin and hematocrit between 2 groups (P>0.05). Conclusions The MPCNL in treatment of children′s middle and upper segment ureteral calculi has short operation time, high calculi clearance rate of the first phase, and low incidence of perioperative complication. Compared with URSL, the URSL is safe and efficient, and it is worthy of clinical application.