Background Urolithiasis is a prevalent disease worldwide with high recurrence rate, minimally invasive interventions have largely replaced open ones, namely PCNL and RIRS. Miniaturization, optical improvements, and modern laser types made these procedures safe and effective in the management of single renal stones. Aim of the study : Is to compare the effectiveness of mini PCNL with RIRS in the treatment of single renal stone of ≤25 mm. Patients and methods This prospective study that included 60 patients with single renal stones of ≤25 mm and were treated by either mini PCNL (group A) or RIRS (group B). The study was performed during the period from October 2020 to April 2021. Results The mean operative time RIRS group was 43.6 ± 10.493, while for miniPCNL it was 36.6 ± 7.035 (P = 0.004). The stone free rate in RIRS and miniPCNL group was 70% and 90% respectively (P = 0.053). The need for JJ stent was higher in RIRS compared to miniPCNL group (70% vs. 40%) respectively (P = 0.02). The duration of hospital stay in miniPCNL was 38.2 h compared to 16.7 h for RIRS group (p = 0.0001). The rate of postoperative hemoglobin drop was higher in MiniPCNL compared to RIRS (P = 0.0001). There was no significant difference regarding complication rates between both groups. Conclusion Mini-PCNL FOR the treatment of renal stones sized ≤25 mm has high stone free rate, shorter operative time, less requirement for JJ stent and near similar post-operative pain and complications compared to RIRS.