Objective To compare the outcomes of mini percutaneous nephrolithotomy (mPNL) and retrograde intrarenal surgery (RIRS) for the management of 2-3 cm lower pole renal calculi (LPC) in obese patients. Patients and methods 120 obese patients with 2-3 cm LPC were randomly divided into mPNL group and RIRS group. Demography, clinical characteristics, perioperative complications, and stone free rate (SFR) were recorded. Stone-free status means no stone on computed tomography 3 months after surgery, or residual fragments were less than 3 mm. Results Baseline characteristics were similar between the two groups. The mean stone burden was 585.39 +/- 131.06 mm(2) in the mPNL group and 548.64 +/- 123.55 mm(2) in the RIRS group (P = 0.125). The SFR of mPNL group was significantly better than that of RIRS group (86.2% vs 61.4%, P = 0.002). Besides, the overall complication rate was 22.4% in the mPNL group and 7% in the RIRS group (P = 0.02). Patients performed with mPNL required longer length of hospital stay than those with RIRS (P = 0.001). There were no significant differences in operative time and stone composition between the two groups. Conclusion In our study, both mPNL and RIRS are safe and effective techniques for the treatment of 2-3 cm LPC in obese patients. Compared to RIRS, mPNL has better SFR at the expense of the higher incidence of complications and prolonged length of hospital stay.