Inertial cavitation may cause hazardous bioeffects during microbubble mediated sonothrombolysis. The purpose of this study was to investigate the influence of ultrasound pulse length and temporal bone on inertial cavitation thresholds within the brain utilizing transtemporal imaging transducers. A pig temporal bone overlaid with muscle tissue was placed over silastic tubing containing a dilute microbubble infusion (1% Definity) within Phosphate Buffered Saline at 37°C. A 1.6 MHz Philips iE33 two-dimensional probe (S5-1) imaged at incremental peak negative pressures. Broadband noise signals were recorded to characterize inertial cavitation using two 20 MHz passive cavitation detectors. Peak-negative-pressure thresholds of inertial cavitation were approximately 263 kPa and 235 kPa with and without bone for 5 microsecond pulse length, and 217 kPa and 215 kPa with and without bone for 20 microsecond pulse length, respectively. The threshold of inertial cavitation is associated with ultrasound pulse length and temporal bone.