BACKGROUND To compare the safety and efficacy of retrograde intrarenal surgery (RIRS) and modified Ultra-mini percutaneous nephrolithotomy (UMP) in semi-supine combined lithotomy position for the management of 1.5-3.5 cm lower pole renal stones (LPSs). METHODS A total of 63 patients with 1.5-3.5 cm LPSs who underwent RIRS (n = 33) or modified UMP (n = 30) in diameter between January 2017 and January 2019 were analyzed retrospectively. Modified UMP was performed in semi-supine combined lithotomy position and a 9.5/11.5 F ureteral access sheath (UAS) was inserted during the procedure in order to maintain low pelvic pressure and to facilitate the removal of stone fragments. Base-line parameters, stone characteristics, illness condition, operation time, postoperative hemoglobin (Hb) drop, postoperative creatinine (Cr) elevation, length of hospital stay, length of postoperative hospital stay, stone-free rate (SFR) and complications were compared between the two groups. RESULTS There were no significant differences between the two groups in base-line parameters, stone characteristics and illness condition. The mean operating time of RIRS group was longer than UMP group (95.61 ± 21.9 vs. 55.0 ± 16.1 min, p < 0.001). The mean postoperative Hb drop was less in RIRS group (7.42 ± 4.7 vs. 15.70 ± 9.8 g/L, p < 0.001). The length of hospital stay and postoperative hospital stay for RIRS were shorter than UMP (4.76 ± 1.1 vs. 5.83 ± 0.8 d, p < 0.001, 2.97 ± 0.9 vs. 4.07 ± 0.9 d, p < 0.001). The Early SFR was higher in UMP group (54.5 vs. 80.0%, p < 0.050) while SFR at 1-month and 3-months postoperatively was similar in both groups (p = 0.504, p = 0.675). There were no significant differences between the two groups in complications (p = 0.228). CONCLUSIONS For patients with 1.5-3.5 cm LPSs, both modified UMP and RIRS are safe and viable. The modified UMP technique was used in this study, application semi-supine combined lithotomy position and the retention of UAS can improve the surgical efficiency and maintain low pressure perfusion in the kidney, which resulted in superior treatment efficacy. Therefore, we highly recommend this technique for LPSs with heavy stone burdens.