Objective To evaluate the efficacy and safety of super-mini percutaneous nephrolithotomy(SMP)and standard percutaneous nephrolithotomy(sPCNL)in the treatment of 2-4 cm renal calculi, so as to provide reference for the management of medium-sized renal calculi. Methods A retrospective analysis was conducted on 168 patients with 2-4 cm renal calculi who underwent either SMP or sPCNL at our hospital during Sep. 2020 and Mar. 2025. The patients were divided into the SMP group(n=85)and sPCNL group(n=83). The baseline characteristics, stone features, operation time, perioperative complications, transfusion rate, postoperative hemoglobin drop, pain score, hospital stay, and stone-free rate(SFR)were compared between the two groups. Results There were no significant differences in baseline characteristics, stone features, and SFR between the two groups(P＞0.05). Compared to the sPCNL group, the SMP group had a longer operation time [(71.76±22.49)vs.(64.22±15.01)min, P=0.034]. However, it had lower postoperative pain score [(2.51 ±0.85)vs.(4.11±0.47), P＜0.001], shorter hospital stay [(3.16±1.45)vs.(4.30±1.06)days, P＜0.001], lower hospitalization costs [(19982.67±4267.80)vs.(21688.53±4575.74)RMB, P=0.004], a slighter decrease in hemoglobin [(6.64±10.56)vs.(12.22±11.50)g/L, P=0.032], and a significantly higher tubeless rate(83.53% vs. 0%, P＜0.001). There was no statistically significant difference in the overall complication rate between the two groups(P＞0.05). Conclusion For 2—4 cm renal calculi, SMP achieves a comparable SFR as sPCNL. Although the operation time with SMP is slightly longer, it offers significant advantages, including reduced postoperative pain, shorter hospitalization, lower costs, less bleeding, and a higher tubeless rate. SMP is a valuable technique worthy of broader clinical application.