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Introduction: The objective of this study is to compare the safety and efficacy, through the stone-free rate (SFR), as well as the costs, between retrograde intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PCNL), for 2-4 cm kidney stones., Material and Methods: We analysed the data relating to RIRS and PCNL performed in 3 reference centres for kidney stones, in the period between 1/2019 and 12/2021. The total number of procedures was 130 (63 RIRS and 67 PCNL). We defined SFR as the absence of lithiasic fragments or stones <3 mm. Results were compared between 2 groups depending on the stone size: 2-3 cm stones (group 1) and >3 cm stones (group 2)., Results: The duration of RIRS was 90 minutes for group 1 and 115 minutes for group 2, and for PCNL it was 135 minutes for group 1 and 145 minutes for group 2. RIRS had shorter duration with a significant difference in group 1 (p = 0.000014). SFR for RIRS was 78% for group 1 and 21% for group 2, and for PCNL it was 92% for group 1 and 81% for group 2. Therefore, there is a statistically significant difference, which is more evident for 3 cm and multiple stones (p = 0.0057 for group 1, p = 0.000146 for group 2). The difference in costs was estimated by calculating the expected costs for a single surgical procedure and the estimated cost per day for ordinary hospitalization., Conclusions: 2-4 cm stones can be safely treated with both RIRS and PCNL, but RIRS should not be chosen as an option for stones >3 cm, except in selected cases. PCNL remains the gold standard for the treatment of complex stones, especially for stones >3 cm. Risk of postoperative complications is higher in PCNL, even if this difference is not great. The costs associated with RIRS, even when recalculating with the need for new treatments, remain cheaper., Competing Interests: The authors declare no conflicts of interest., (Copyright by Polish Urological Association.)