Background: The optimal management of medium sized renal stones differs from one patient to another according to different factors. Stone attenuation value (SAV) is one of these factors which affect stone free rate (SFR) after extracorporeal shock wave lithotripsy (ESWL) with limited effect on mini-percutaneous nephrolithotomy (mini-PCNL). Objective: To compare safety and SFR of mini-PCNL and ESWL in the treatment of non-lower pole renal stones with high density and size of 10-20 mm. Patients and Methods: This prospective randomized study was carried out at Sayed Galal, Al Azhar University Hospital, Cairo, Egypt from November 2019 to October 2020 and included 70 patients with non-lower pole renal calculi 10 to 20 mm. Patients were randomly allocated in 2 equal groups: Group A was treated by mini-PCNL and group B was treated by ESWL. The primary end point was SFRs (no stone or residual 3>mm) in ESWL and mini-PCNL in this category of stone. The secondary end points were the complication rate, retreatment rate, and need for auxiliary procedures in each group. Results: The overall operative time was significantly lower in mini-PCNL group (median: 50.00; IQR: 20.00) compared to ESWL group (median: 55.00; IQR: 28.00) (p= 0.001). The overall fluoroscopy time was significantly lower in mini-PCNL than ESWL (3.2 versus 3.6 minutes, p=0.040). In mini-PCNL group, 32 out of 34 (94.1%) patients were stone free. In ESWL group, 10 out of 33 (30.1%) were rendered stone free after the third ESWL session. The SFR was significantly higher in mini-PCNL group (p < 0.001). In mini-PCNL group, none of cases needed a second look PCNL. The 2 failed cases had significant residual fragments that migrated into inaccessible calyx during pneumatic lithotripsy. In ESWL group, all cases had normal hemoglobin (Hb) level at each follow-up visit. In mini-PCNL group, when comparing pre- and post-operative Hb, a very highly significant differences were observed between pre- and post-operative Hb level (p < 0.001). Conclusions: Mini-PCNL is superior to ESWL in treatment of non-lower pole medium sized renal stones of high density with high SFR, and low complication rate as need for re-hospitalization or need for auxiliary procedure.