Objective: To determine how sheath and endoscope size affect intrarenal pelvic pressures and risk of postoperative infectious complications comparing "Mini" vs "Standard" percutaneous nephrolithotomy (PCNL). Materials and Methods: Uropathogenic Escherichia coli were grown and 109 of them were instilled into the porcine renal pelvis through retrograde access for 1 hour. Percutaneous access utilized a 14/16F 20 cm ureteral access sheath for the Mini arm and a 30F sheath for the Standard arm. Nephroscopy was simulated utilizing either an 8/9.8F semirigid ureteroscope or 26F nephroscope for 1 hour while intrarenal pelvic pressure was continuously monitored. Blood and tissue cultures of kidney, liver, and spleen biopsies were plated and incubated and positive cultures were confirmed with polymerase chain reaction. Results: Intrapelvic pressures were higher in the Mini group, 18.76 ± 5.82 mm Hg vs 13.56 ± 5.82 mm Hg (p < 0.0001). Time spent above 30 mm Hg was greater in the Mini arm, 117.0 seconds vs 66.1 seconds (p = 0.0452). All pigs had positive kidney tissue cultures whereas spleen cultures were positive in 100% and 60% of pigs in the Mini and Standard arms, respectively (p = 0.0253); 90% and 30% had positive liver tissue culture in the Mini and Standard arms, respectively (p = 0.0062). Blood cultures were positive in 30% of pigs in the Mini arm compared with none in the Standard arm (p = 0.0603). Conclusion: Mini-PCNL was associated with higher intrarenal pressures and higher risk of end organ bacterial seeding in the setting of an infected collecting system. This suggests a higher potential for infectious complications in a clinical setting.