To assess the functional effects of percutaneous nephrolithotomy (PCNL) and its outcomes in the operated kidney, we prospectively studied 30 consecutive cases undergoing PCNL. Kidney function was evaluated preoperatively and 3 months after surgery with serum creatinine, glomerular filtration rate (GFR), and with (99m)Tc-DMSA SPECT-CT scans to determine the differential renal function (DRF). PCNL effects in the operated kidney DRF were considered globally (DRFPLANAR, DRFSPECT) and in the region of percutaneous access (DRFACCESS). PCNL functional impact was also assessed depending on its outcomes, namely success (stone-free status) and the development of perioperative complications. PCNL has rendered 73 % of the cases completely stone free with a 33 % complication rate. After PCNL, serum creatinine and GFR did not change significantly, whereas DRFPLANAR and DRFSPECT dropped 1.2 % (p = 0.014) and 1.0 % (p = 0.041), respectively. The highest decrease was observed in DRFACCESS (1.8 %, p = 0.012). Stone-free status after PCNL did not show any impact on kidney function. Conversely, cases that suffered from a complication showed impairment in serum creatinine (0.1 mg/dL, p = 0.028), in GFR (11.1 mL/min, p = 0.036) as well as in DRFPLANAR (2.7 %, p = 0.018), DRFSPECT (2.2 %, p = 0.023) and DRFACCESS (2.7 %, p = 0.049). We conclude that PCNL has a minimal impact on global kidney function, which is mainly located in the region of percutaneous access. The advent of perioperative complications increased PCNL functional damage, whereas the stone-free status did not show any meaningful effect.