Abstract Extracorporeal shockwave lithotripsy (SWL) revolutionized the treatment of urinary stones when first introduced three decades ago. Instead of open stone surgery, acoustic energy could be applied from outside the body to fragment stones in situ. Although widely utilized for treatment of stones, SWL has not fully lived up to its potential. Incomplete fragmentation of stones can result in significant pain (when fragments migrate down the ureter and obstruct urine outflow) and a high rate of residual fragments that need subsequent additional therapy. SWL research has shown the complex role of acoustic cavitation in the stone comminution process. While cavitation has been demonstrated to be an essential component of the fragmentation process, the bubbles produced also interfere with subsequent shockwaves reducing their effectiveness and sometimes causing tissue injury. SWL treatments at extremely low rates (i.e. <30 shocks/min) have been shown in the laboratory to be substantially more efficient and cause less tissue injury because there is sufficient time for most of the cavitation bubbles to dissolve. However, ultra-low rates have not been adopted clinically because of the impractically long procedure times that would be required. We have previously demonstrated that unfocused low amplitude acoustic bursts can stimulate rapid coalescence and dispersion of cavitation bubbles during SWL clearing the pathway for subsequent shockwaves within tens of milliseconds. By this method we can recover the stone fragmentation efficiency and safety of very low shockwave rates at standard clinical rates. Initial studies outlined in this proposal are designed to optimize the bubble coalescence and dispersion process for use with a standard clinical electromagnetic shockwave lithotripsy system. The following studies will then demonstrate safety and improved efficacy on a porcine model such that a pilot clinical trial could be initiated following this work.