Objective: To evaluate the efficacy and safety of mini percutaneous nephro-lithotripsy (mini PCNL) and retrograde intrarenal surgery (RIRS) in treatment of renal stones larger than 20mm in its longest diameter. Patients & Methods: In a prospective randomized study including 40 patients divided into two groups each 20 patient. Group A included 12 males and 8 females with age ranged from 15 to 62 years had mini PCNL for renal pelvic and calyceal stones. Group B included 8 males and 12 females with age ranged from 18 to 65 years old had RIRS. Flexible ureteroscopy was used for pelvic and calyceal stones using holmium:YAG laser (dusting approach). In both groups the procedure outcome in terms of Operative time, Blood loss, hospital stay, complications using modified Clavien grading system , the need of auxiliary procedures , stone free rates after 3 weeks by using CTUT, were evaluated statistically. Results: Statistical analysis of the data showed that there was insignificant difference between the {mean ± SD} of the BMI in patients of group A which was {27.850±3.183} kg/m2; while in patients of group B was {29.700±7.927} kg/m2 . Regarding stone size, there was insignificant difference between the {mean ± SD} of group A which was 2.57±0.22mm, while in group B was 2.6±0.24mm. Regarding the operative time the {mean ± SD} of group A was 104.43±14.79 minutes which was significantly (P