To assess outcomes of supracostal ultrasound guided approach percutaneous nephrolithotomy (SUGA-PNL) and retrograde intrarenal surgery (RIRS) in isolated large volume upper calyceal stones (UCS). This was a prospective randomized study including patients with isolated UCS > 20mm. The patients were randomized into two groups: group (P) (SUGA-PNL) and group (R) (RIRS). Patients’ demographics, stones characteristics, operative, and postoperative outcomes essentially the stone free rate (SFR) and complications rate were documented. The stone clearance was defined as no fragments or residual fragments less than 2mm in the one month non contrast CT scan follow up. Eighty-nine patients opted to undergo the procedure according to the preoperative randomization. Four patients, 2 patients from each group, lost to follow up and other 2 patients were excluded from group (R) due to a tight ureter. Both groups were comparable as regards the preoperative demographics and stone characteristics. There were statistically significant differences regarding total operative time, the change in hemoglobin level, and postoperative pain score (P: 0.024, 0.010 and 0.032 respectively). The SFR was 88.1% in group (P) compared to 73.2% in group (R) (P: 0.019). Moreover, it did not differ significantly between both groups regarding the intraoperative and postoperative complications. No visceral and thoracic injuries were documented in group (P). On other side, 6 patients (14.6%) from group (R) had different grades of ureteral injury during access sheath placement. SUGA-PNL is a safe and effective treatment modality for UCS > 20mm with a higher SFR than RIRS.