OBJECTIVE To compare the outcomes of percutaneous nephrolithotomy (PNL) and extracorporeal shock wave lithotripsy (ESWL) for moderate sized (1-2 cm) upper and middle pole renal calculi in regards to stone clearance rate, morbidity, and quality of life. METHODS All patients diagnosed with moderate sized upper and middle pole kidney stones by computed tomography (CT) were offered enrollment. They were randomized to receive either ESWL or PNL. The SF-8 quality of life survey was administered preoperatively and at 1 week and 3 months postoperatively. Abdominal radiograph at 1 week and CT scan at 3 months were used to determine stone-free status. All complications and outcomes were recorded. RESULTS PNL established a stone-free status of 95% and 85% at 1 week and 3 months, respectively, whereas ESWL established a stone-free status of 17% and 33% at 1 week and 3 months, respectively. Retreatment in ESWL was required in 67% of cases, with 0% retreatment in PNL. Stone location, stone density, and skin-to-stone distance had no impact on stone-free rates at both visits, irrespective of procedure. Patient-reported outcomes, including overall physical and mental health status, favored a better quality of life for patients who had PNL performed. CONCLUSIONS PNL more often establishes stone-free status, has a more similar complication profile, and has similar reported quality of life at 3 months when compared with ESWL for moderate-sized kidney stones. PNL should be offered as a treatment option to all patients with moderate-sized kidney stones in centers with experienced endourologists.