Background: Percutaneous nephrolithotomy (PNL) is a procedure that has traditionally been performed in an inpatient or hospital setting. Many surgical procedures have evolved over time from an inpatient/hospital setting to outpatient procedures performed in surgical centers. Outpatient PNL has become an accepted standard in select patients, but to date, the procedure has not been performed in an outpatient surgical center. Case Presentation: We describe our initial experience managing large renal stone burden with PNL performed completely outpatient in a freestanding ambulatory surgery center. The patient was carefully selected as a young, healthy, thin patient with straightforward renal stone burden and favorable anatomy per CT. Access was achieved with a combination of fluoroscopic and endoscopic needle guidance. The procedure was performed with several modifying factors to enable an effective outpatient discharge. Conclusion: Our experience reinforces the outpatient feasibility of PNL and incites the possibility of transitioning the procedure to an ambulatory surgical center in select patients to provide healthcare savings and an improved patient experience.