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PURPOSE To evaluate the safety and efficacy of new generation super-mini percutaneous nephrolithotomy (New-SMP) in the treatment of ≥20 mm renal stones. METHODS We retrospectively analyzed the New-SMP procedures (14F) performed in the cases with ≥20 mm renal stones between April 1, 2016 and July 1, 2018. The cases with ipsilateral Double-J stent and/or nephrostomy tube preoperatively, ipsilateral ureteral stone, uncorrected coagulopathy, active urinary tract infection, congenital abnormalities, and urinary diversion were excluded. RESULTS Of totally 188 included cases, 8 (4.3%) were children (≤14 years) and 180 (95.7%) were adults. The cases had a mean age of 47.14 ± 15.13 years, a mean stone size of 31.57 ± 9.8 mm, and a mean S.T.O.N.E score of 7.02 ± 0.73. The New-SMP took a median operative time of 35 minutes (range 6-127). A total of 173 (92%) cases received single-access-tract procedure. The drop in hematocrit was 14.62 ± 8.36 g/L after the procedure. The serum white blood cells (WBCs) increased to 2.58 ± 2.89 × 109/L. The mean hospital stay was 2.4 ± 1.5 days. New-SMP had a stone-free rate of 84% within 48 hours and 91.5% at 3 months postoperatively. Five (2.7%) cases required auxiliary procedures. The tubeless rate was 87.2%, including 44.1% cases with total tubeless, 41.5% cases with Double-J stent, and 1.6% cases with ureteral catheter. Totally 9.6% cases got fever (>38°C), 1.0% cases had urosepsis, and no cases developed shock. In addition, no transfusion and arterial embolization were required. CONCLUSIONS New-SMP could be a safe and efficacious approach for the management of ≥20 mm renal stones. The novel modified technique and system may extend the indication of SMP to large renal stones. Further clinical studies and direct comparisons between New-SMP and other available modalities of percutaneous nephrolithotomy are required.