Objective: Management of patients with upper ureteral and renal urolithiasis is challenging for endourologists. Since the advancements in endourological equipment/devices, retrograde intrarenal surgery (RIRS) has become an attractive, widespread technique for upper urinary tract stone manipulation, owing to its advantage of being noninvasive with higher stone clearance rate and less pain compared with traditional shock wave lithotripsy (SWL) and percutaneous nephrolithotripsy (PNL). However, the outcome and complication of staged RIRS for large stone burden (> 2.0 cm) management for renal stones still need to be reported. A total of 172 cases of renal calculi were treated by RIRS in a single center; among these, 22 had renal stone size larger than 2.0 cm. In this work, we present our experience and treatment outcomes of these patients. Materials and methods: Between August 2015 and January 2016, we enrolled 172 patients with upper urinary tract calculi who underwent RIRS with holmium laser lithotripsy performed by one surgeon in a singer center. Based on a medical record review, we collected data pertaining to the outcomes and complications of RIRS. Results: A total of 172 patients with upper urinary tract stones were included in this study (113 male and 59 female patients). All patients underwent RIRS with holmium laser lithotripsy procedure. The overall stone-free rate (SFR) was 90.6%. The average stone size was 0.8 cm with average operation time of 89.7 minutes. Average hospital stay was 2.7 days. The average pain score was 2.38/10 by the Numerical Rating Scale. In the large stones size subgroups, the SFR of stone burden between 2.0 cm and 3.0 cm was 80.2%, and the SFR of stone burden over 3.0 cm was 45.0% by single RIRS. Ten of 22 patients underwent two-staged RIRS and their SFR improved from 45.0% to 76.5%. No major complications (Clavien III–V) were noted in the study groups. Conclusion: To the best of our knowledge, RIRS for large renal stone manipulation is an effective and safe treatment modality currently. In our study, the single RIRS SFR was superior to PNL or SWL even when the stone burden was between 2.0 cm and 3.0 cm (80.2%). For those patients whose stone burden was over 3.0 cm or for those with comorbidities, staged RIRS resulted in a lower complication rate, reduced hospital stay, and better SFR (76.5%).