To investigate the feasibility and initial outcomes of a combination of ureterorenoscopy (URS) using holmium laser lithotripsy and extracorporeal shockwave lithotripsy (SWL) in a single outpatient session for the treatment of large renal stone burdens in patients refusing or unsuitable for percutaneous nephrolithotomy (PCNL). Fourteen patients with a mean age of 52.7 years (range 34-81 years) having a mean stone burden of 847 mm2 (range 58 mm2-1850 mm2) were treated with combined URS laser lithotripsy and SWL as an alternative to PCNL. The SWL (mean 2800 shockwaves) was performed using the Storz Modulith SL-X, and flexible URS with holmium laser lithotripsy was performed either during or following SWL. Ninety-three percent of the patients (13/14) were treated successfully on an outpatient basis. Two patients were rendered stone free after the initial procedure alone (14%). Overall, including secondary outpatient treatment with a second session of URS alone (N = 7) URS and SWL (N = 1), SWL (N = 1), or oral alkalinization therapy (N = 1), the stone-free rate was 76.9% (10/13). One patient was excluded secondary to death from unrelated causes after the initial procedure, and the success rate (residual fragments <4 mm) was 84.6% (11/13). The two treatment failures included one patient who required a third URS procedure and one patient who developed urosepsis necessitating nephrostomy-tube placement who underwent subsequent PCNL. In comparison with traditional approaches using PCNL and second-look nephroscopy, single-session combined URS and SWL with a second outpatient procedure may offer equivalent results with decreased morbidity in carefully selected patients.