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Objective: To investigate the outcomes of retrograde intrarenal surgery (RIRS) for large renal calculi, and to identify factors that influence the stone-free rate after RIRS for renal stone burden greater than 2 centimeters. Materials and Methods: This retrospective chart review included patients who underwent RIRS for renal calculi greater than 2 centimeters in size during January 2015 to December 2016 at Siriraj Hospital Thailand's largest national tertiary referral center. Data were collected and compared between those having and not having residual stones greater than 2 cm in diameter. Results: The present study included 100 eligible cases. The most common site was at lower calyces (42%). The mean stone burden size was 31.43 mm (range: 20 to 140). The average operative time was 62 minutes (range: 20 to 150), and the mean hospital length of stay was 2.7 days (range: 1 to 22). The most common stone composition was calcium oxalate monohydrate (37%), followed by calcium phosphate (23%). The success rate was 84% and 94% after the 1st session and 2nd session of RIRS, respectively. The factors that were found to predict residual stone after RIRS were stone burden greater than 35 mm in size (odds ratio [OR]: 5.86, 95% confidence interval [CI]: 1.77 to 19.57; p = 0.004) and lower pole location (OR: 1.97, 95% CI: 1.039 to 3.742; p = 0.038). Sepsis was found in 6 patients, all of whom were successfully treated with intravenous antibiotic, except for one mortality in an immunocompromised patient. Conclusion: RIRS is a promising treatment option for renal calculi with large stone burden. Large kidney stones (>2 cm) can be treated with high success rate and low morbidity. The most significant predictors of residual calculi are stone burden more than 35 millimeters in size and lower pole location. [ABSTRACT FROM AUTHOR]