BackgroundTo compare the efficacy and safety of standard percutaneous nephrolithotomy (PCNL) with mini- PCNL for kidney stones 2–4 cm.MethodsEighty patients were enrolled in a comparative study, they were randomly divided into mini-PCNL group (n = 40) and standard-PCNL (n = 40). Demographic characteristics, perioperative events, complications, stone free rate (SFR) were reported.ResultsBoth groups showed no significant difference in clinical data about age, stone location, back pressure changes, and body mass index. The mean operative time was (95 ± 17.9 min) in mini-PCNL, and (72.1 ± 14.9 min). Stone free rate were 80% and 85% in mini-PCNL and standard-PCNL respectively. Intra-operative complications, post-operative need for analgesia, hospital stay were significantly higher in standard-PCNL compared to mini-PCNL (85% vs. 80%). The study followed CONSORT 2010 guidelines for reporting parallel group randomization.ConclusionMini-PCNL is an effective and safe treatment of kidney stones 2–4 cm, it has the advantage over standard-PCNL being has less intra-operative events, less post-operative analgesia, shorter hospital stay, while operative time and stone free rate are comparable when considering multiplicity, hardness, and site of stones.