Objective: To compare the outcomes in patients who have been treated with percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS) on renal stones between 2–4 cm in diameter. Methods: We evaluated patients who underwent PCNL or RIRS for 2–4 cm renal stones between January 2014 and January 2018 in the First Affiliated Hospital of Harbin Medical University. Stone size, operation, hospitalization time, success rates, stone-free rates and complication rates were compared in both groups. Patients were followed for three months. Results: A total of 178 patients were in the PCNL group; 152 patients were in the RIRS group. In the RIRS group, the mean operation time was significantly higher than PCNL group. The postoperative hospitalization time, amount of bleeding and post-operative VAS were significantly higher in PCNL group. The serum creatinine of both groups was increased after operation, but the difference was not statistically significant. The stone-free rate was 89.89% for the PCNL group and 81.6% for the RIRS group after first procedure. No major complications (Clavien III–V) occurred in the RIRS group. The stone-free rate of PCNL group after the first operation was higher than that of RIRS group. Conclusion: Although the primary treatment method for renal stones ≥2 cm size is PCNL, serious complications can be seen. Therefore, RIRS can be an alternative treatment option in the management of renal stones between 2–4 cm in diameter.