We evaluate the outcomes of ureteroscopy vs prone mini-percutaneous nephrolithotomy for 1-2-cm renal stones using a 2-group parallel randomized control trial. Adult patients presenting with renal stones between 1 and 2 cm were randomized. Exclusion criteria included solitary kidney, multiple stones, and comorbidities precluding prone positioning. Block randomization was performed and was opened to the surgeon the morning of the procedure. Stone-free rate was evaluated by computed tomography 1-30 days postoperatively. Complications, re-treatment rates, and costs were evaluated. A total of 51 mini-percutaneous nephrolithotomy and 50 ureteroscopy patients were included. Baseline demographics were similar. Using a 2-mm cutoff, stone-free rate was higher in the mini-percutaneous nephrolithotomy group (76 vs 46%, P = .0023). The residual stone burden was significantly higher in the ureteroscopy group than the mini-percutaneous nephrolithotomy group (3.6 vs 1.4 mm, P = .0026). Fluoroscopy time was significantly higher in the mini-percutaneous nephrolithotomy group (273 vs 49 seconds, P < .0001). There were no differences in postoperative complications within 30 days, the necessity of a secondary procedure within 30 days, and pre- to postoperative creatinine change (P > .05). Surgical time did not vary significantly (P = .1788). Average length of stay was higher in the mini-percutaneous nephrolithotomy group (P < .0001). Both net revenue and direct costs were higher in mini-percutaneous nephrolithotomy procedures (P < .05), though they offset each other with a nonsignificant operating margin (P = .2541). In a prospective, randomized, controlled clinical trial using a 2-mm residual stone burden cutoff, mini-percutaneous nephrolithotomy was more likely to render patients stone-free than flexible ureteroscopy. Complications, surgical times, and operating margins did not vary between the approaches.