Background: Renal stones for patients with a single functioning kidney are considered a great challenge for urologists. Different treatment modalities are used for those with a single functioning kidney, including shock wave lithotripsy, retrograde intra-renal surgery and percutaneous nephrolithotomy (PCNL). This study aimed to compare the effectiveness and safety outcomes of PCNL in patients with a single kidney compared to those with bilateral kidneys. Methods: A prospective comparative study conducted in Urology department of Safeer Al-Imam Al-Hussein hospital in Karbala city-Iraq through the period from 1 st of March, 2015 to 30 th of September, 2018 on sample of 173 patients with renal stones surgically operated with PCNL categorized into two groups; group I included 51 patients with a single functioning kidney and group II included 122 patients with bilateral functioning kidneys. Results: The mean age of group I patients was 42.76 years which was significantly higher than mean age of group II patients of 36.54 years (p=0.01). No significant differences were observed between group I and group II patients regarding gender, pre and intraoperative characteristics. Postoperative stone clearance, bleeding, renal function, organ injury and sepsis were not significantly different between two. Conclusions: PCNL is effective and safe surgical procedure for treatment of renal stones of patients with a single functioning kidney.