Invivo experiments were conducted to demonstrate the feasibility of HIFU application to control postliver biopsy hemorrhage. Yorkshire pigs were anesthetized and their livers were surgically exposed. Core biopsies (n=74) were performed on the exposed hepatic parenchyma with 14‐gauge (n=41) and 18‐gauge (n=33) core biopsy needles that were inserted 1.5–2 cm deep into the liver. Hemorrhage was determined from the weight of the blood collected from each biopsy puncture site using surgical sponges immediately after biopsy needle retraction. To stop hemorrhage, immediate HIFU was applied to the needle entry site (n=44) after needle retraction. HIFU was generated using a piezoelectric (PZT) transducer (diameter=42 mm, F number=1.2) at 4.23 MHz. Whole‐blood clotting times were measured at various times throughout the experiments. Mean blood loss from control biopsy sites using a 14‐gauge needle (n=18) was 1.78 g, while mean blood loss using an 18‐gauge needle (n=10) was 1.22 g (two 14‐gauge‐needle control biopsies were excluded). Virtually no blood loss was measured from the biopsy needle entry site after HIFU application for both 14‐ and 18‐gauge‐needle biopsies. Ultrasound imaging demonstrated a marked difference between control sites and HIFU‐treated sites where successful hemostasis was achieved.