Cavitation-based ultrasound histotripsy has shown potential for treating infections on surgical mesh. The goal of this paper was to explore a new scan strategy while assessing the impact of scan speed, scan step size, and the number of cycles in the tone burst on the destruction of S. aureus biofilms grown on surgical mesh samples using ultrasound histotripsy pulses (150 MPa/-17 MPa). For each exposure, the number of colony forming units (CFUs) on the mesh and released onto the surrounding gel was quantified. Most of the exposed mesh samples had no CFUs, and there was a statistically significant reduction in CFUs on the mesh for each of the exposures, with an average reduction of 3.8 log10 relative to the sham. Compared with the sham, there was also a statistically significant reduction in CFUs on the gel with the highest exposures.