Introduction and Importance:Staghorn calculi (SC) are defined as large kidney stones that fill the renal pelvis and at least one renal calyx. They represent 10–20% of all renal stones in developing countries and require prompt diagnosis and management. Massive SC (over 5 cm) are treated exclusively via open surgery, despite percutaneous nephrolithotomy (PCNL) being the gold standard treatment for large stones. Descriptions of PCNL for massive SC are very limited in the literature.Case Presentation:We report a case of a 63-year-old male who presented with chronic abdominal pain, hepatosplenomegaly, and normal renal function. He was later diagnosed with polycythemia vera. Computed tomography of the abdomen revealed massive, bilateral staghorn stones measuring 7.3×5.5 cm and 1.8×4.5 cm on the right and left, respectively. Additionally, the right stone was found to be compressing the inferior vena cava (IVC). The patient was promptly scheduled for right-sided PCNL and the target of 80% stone fragmentation was successfully attained.Discussion:We present the first case of a stone of such size in the Middle East, as well as the first known case of a renal stone compressing the IVC. Unlike previous reports, the stone was successfully fragmented via PCNL – a procedure that has not been described for stones of such size.Conclusion:This report highlights that ultrasound-guided PNCL without any other intervention is sufficient for the successful treatment of giant SC. Greater research is needed on the potential utility of using ultrasound-guided PCNL for the fragmentation of stones sized over 5 cm.