The objective of the study is to compare the efficacy and safety of extracorporeal shock wave lithotripsy (ESWL) and mini-percutaneous nephrolithotomy (MPCNL) in treating renal stones sizing 15-25 mm in infants <3 years. Forty-six infants with renal stones sizing 15-30 mm were treated by either ESWL (22 renal units in 22 infants) using Dornier compact delta lithotripter or MPCNL (25 renal units in 24 infants) using 14F-18F renal access under general anesthesia. The operation time, stone-free rate, re-treatment rate, and complications between the two groups were compared with the χ(2), Mann-Whitney U, and Student's t tests. No significant differences in mean age and stone size were observed between the two groups. The 1- and 3-month postoperative stone-free rates were 84 and 96% in MPCNL group and were 31.8 and 86.4% in ESWL group. The re-treatment and complication rates were significantly higher in ESWL group than in MPCNL group (50 vs. 12%, P = 0.004; 16.0 vs. 45.5%, P = 0.028). The stone recurrence rate was similar between the two groups. No significant changes of serum creatinine (Cr) level and glomerular filtration rate were observed in both groups. In conclusion, MPCNL is an effective and feasible alternative monotherapy for large renal stones (15-25 mm) in infants, with a higher stone-free rate and a lower complication rate when compared with ESWL.