INTRODUCTION: Multiple studies have concluded that ambulatory percutaneous nephrolithotomy (aPCNL) is safe. However, selection criteria remain vague and no investigators have assessed the practicality of using various post-procedural drainage strategies in the ambulatory setting. In this study we establish a set of inclusion and exclusion criteria for aPCNL, compare outcomes between aPCNL patients and those admitted following PCNL, and incorporate a variety of "exit" strategies including Double-J stent, ureteropelvic junction (UPJ) stent and totally tubeless techniques. METHODS: We developed inclusion and exclusion criteria to determine patient eligibility for aPCNL. Between January 2014 and December 2016, 52 out of 145 patients met criteria for aPCNL and 47 of these patients were ultimately discharged on the same day. Forty-seven of the remaining 98 patients who were admitted following PCNL were randomly selected as a control group. Primary outcomes included stone-free status, emergency department (ED) visits and hospital readmissions within the 6-week post-operative period. Statistical analysis was performed using Student's t-tests, chi square tests, and Fischer's exact tests. RESULTS: Both groups had similar age (P = 0.91), sex (P = 0.68), body mass index (P = 0.91), and stone burden (P = 0.12). Patients in the ambulatory group had a lower Charlson Comorbidity score (aPCNL CCS = 0.11, inpatient PCNL CCS = 0.62, P = 0.002). Seventy three percent of ambulatory patients and 62% of standard PCNL patients had no residual stone burden 6 weeks following PCNL (P = 0.33). The average residual stone fragment in our ambulatory and standard PCNL group was 3.5 and 3.2 mm, respectively. Five patients (11%) from the aPCNL group and 4 (9%) from the standard PCNL group presented to the ED (P = 0.76). One aPCNL (2%) and three standard PCNL (6%) patients were re-admitted to the hospital (P = 0.62). CONCLUSIONS: In this study we establish specific inclusion and exclusion criteria for aPCNL. Using these criteria we then demonstrated the practicality of using various exit strategies to facilitate aPCNL. Future randomized control trials would be beneficial in confirming the safety and efficacy of aPCNL in select patients.