Histotripsy is a focused ultrasound therapy under development for multiple diseases, including deep vein thrombosis (DVT). Benchtop studies to gauge the efficacy of histotripsy for chronic DVT present a challenge due to pathologic changes in composition that are difficult to replicate in vitro. Tendon is a readily available tissue with an extensive extracellular matrix similar to chronic DVT. This study aims to assess histotripsy-induced changes to tendon at driving parameters effective for acute thrombus ablation. Porcine patellar tendons were bisected into control (N = 19) and treatment (N = 21) segments. Histotripsy pulses were applied for 1 to 20 min at rates of 250 or 500 Hz. The pulse duration (6.7 μs) and peak negative pressure (35 MPa) were previously shown to be effective for acute thrombus ablation. Treated specimens exhibited gross swelling in targeted regions. Manual segmentation of ultrasound images was used to estimate the area of tissue affected by histotripsy, which was found to expand by up to 30% over the exposure durations for both pulsing rates. Histological analysis revealed loss of linear fiber organization and liquefaction within treated regions. Overall, these data indicate histotripsy effectively disrupts tendon integrity, making it a potential tool for the management of chronic DVT.