Large abscesses are walled-off collections of pus and bacteria that often do not respond to antibiotic therapy. Standard of care involves percutaneous placement of indwelling catheter(s) for drainage, a long and uncomfortable process with high rehospitalization rates. The long-term goal of this work is to develop therapeutic ultrasound approaches to eradicate bacteria within abscesses as a noninvasive therapeutic alternative. Inertial cavitation induced by short pulses of focused ultrasound (histotripsy) is known to generate lethal mechanical damage in bacteria. Prior studies with Escherichia coli (E. coli) in suspension demonstrated that bactericidal effects increase with increasing peak negative amplitude, treatment time, and duty cycle. The current study investigated correlates of bactericidal activity with histotripsy cavitation cloud size. Histotripsy was applied to E. coli suspensions in 10-mL sample vials at 810 kHz, 1.2 MHz, or 3.25 MHz for 40 min. The cavitation activity in the sample vials was separately observed with high-speed photography. The cavitation cloud area was quantified from those images. A linear relationship was observed between bacterial inactivation and cavitation cloud size ( R² = 0.98 ), regardless of the acoustic parameters (specifically frequency, pulse duration, and power) used to produce the cloud.