Background: Renal staghorn stones are challenging for urologists to ensure maximum stone clearance and minimal morbidity. Percutaneous nephrolithotomy (PCNL) has become the gold standard treatment for renal staghorn stones. To assess the safety and efficacy of a novel integrated rigid and flexible percutaneous nephroscope(Rigi-flex nephroscope) in PCNL for renal staghorn stones. We present our initial experience with this new technique. Methods: From March to July 2016, a prospective analysis of 3 patients with staghorn stones treated with Rigi-flex nephroscope in PCNL under totally ultrasound guidance by paravertebral block (PVB) anesthesia was done. PCNL was performed with the rigid section of a 13-Fr Rigi-flex nephroscope firstly and the stones were disintegrated into fragments by holmium laser. Then the stones were removed by active flushout, followed by a search for residual stones in other inaccessible calyces with the flexible section. Finally, the residual stones were disintegrated into small fractions by holmium laser in situ or repositioned with a set of disposable retrieval baskets to pelvic or other accessible areas. The whole procedure was accomplished via only one nephrostomy tract. The operating time, stone-free rates (SFR), postoperative hemoglobin drop, complications, length of hospitalization, were recorded. Results: The operation time were 89, 62 and 45 min, respectively, the postoperative hemoglobin drop was 1, 0.8 and 0.9 mg/dl, respectively. The postoperative Kidney-Ureter-Bladder (KUB) radiograph of the three patients showed no residual fragment >3 mm. No patients needed blood transfusion and suffered significant complications. The length of hospitalization was 9, 6 and 4 days, respectively. No patient needed multiple tracts PCNL or staged auxiliary measures one month after the operation. Conclusions: The application of Rigi-flex nephroscope in PCNL under ultrasound guidance for staghorn stones has its unique advantages as monotherapy with increasing procedural stone free rate (SFR) via single nephrostomy tract, hence there is less morbidity as it does not require additional tracts dilation and staged auxiliary procedures combination. However, SFR should also be evaluated at a longer follow-up, particularly for staghorn stone, further large-scale multicenter prospective clinical trial are needed to verify its feasibility.