Renal stones with single functioning kidney are a great challenge facing the urologists. This study aimed to compare the effectiveness and safety outcomes of percutaneous nephrolithotomy in patients with single functioning kidney and in patients with bilateral functioning kidneys. Methods: A prospective comparative study conducted in Urology department of Safeer Al-Imam Al-Hussein hospital in Karbala city, at period from 1st of March, 2015 to 30th of September, 2018. Sample of 173 patients with renal stones surgically operated with percutaneous nephrolithotomy (PCNL) categorized into two groups; group I with single functioning kidney (SFK) and group II with bilateral functioning kidneys (BFK). Results: 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). The PCNL postoperative stone clearance, bleeding, renal function, organ injury and sepsis were not significantly different between group I and group II patients. Conclusion: The percutaneous nephrolithotomy is effective and safe surgical procedure for treatment of renal stones in patients with single functioning kidney.