To improve in vitro lithotripsy models, we investigated the effects of multiple experimental variables on stone fragmentation. We performed timed burst wave lithotripsy (BWL) and shock wave lithotripsy (SWL) exposures in a water tank with the following variable parameters: water gas content (60, 30, and 15% O2), temperature (20 and 37°C), stone holder degree of enclosure (open wire basket, polyvinyl chloride (PVC) open-ended gel, and similar material anatomically accurate artificial kidney), and stone type (Begostone at 2 mixture ratios, calcite, calcium oxalate monohydrate (COM), and uric acid). At least 3 stones were treated for each condition, with fragmentation defined as percent stone mass <2 mm. Begostone (2:1 powder:water ratio) treated with BWL at 20°C vs. 37°C showed 75±13% vs. 62±6% breakage, respectively. Using the same stone type, gas concentrations of 60, 30, and 15% O2 showed breakage of 23±4%, 55±8%, and 82±16%, respectively. More enclosed kidney phantoms showed decreasing lithotripsy efficacy of 94±11%, 64±21%, and 13±2% breakage in basket, PVC, and anatomic phantoms, respectively. 2:1 Begostone most closely mimicked COM stone breakage. SWL exposures produced similar trends. This work indicates the importance of controlling multiple variables during in vitro lithotripsy experiments. [Work supported by NIH P01 DK043881 and K01 DK104854.]To improve in vitro lithotripsy models, we investigated the effects of multiple experimental variables on stone fragmentation. We performed timed burst wave lithotripsy (BWL) and shock wave lithotripsy (SWL) exposures in a water tank with the following variable parameters: water gas content (60, 30, and 15% O2), temperature (20 and 37°C), stone holder degree of enclosure (open wire basket, polyvinyl chloride (PVC) open-ended gel, and similar material anatomically accurate artificial kidney), and stone type (Begostone at 2 mixture ratios, calcite, calcium oxalate monohydrate (COM), and uric acid). At least 3 stones were treated for each condition, with fragmentation defined as percent stone mass <2 mm. Begostone (2:1 powder:water ratio) treated with BWL at 20°C vs. 37°C showed 75±13% vs. 62±6% breakage, respectively. Using the same stone type, gas concentrations of 60, 30, and 15% O2 showed breakage of 23±4%, 55±8%, and 82±16%, respectively. More enclosed kidney phantoms showed decreasing lithotripsy effic...