Rationale and Objectives Acoustic droplet vaporization (ADV) shows promise for spatial control and acceleration of thermal lesion production. The investigators hypothesized that microbubbles generated by ADV could enhance high-intensity focused ultrasound (HIFU) thermal ablation by controlling and increasing local energy absorption. Materials and Methods Thermal lesions were produced in tissue-mimicking phantoms using focused ultrasound (1.44 MHz) with a focal intensity of 4000 W · cm −2 in degassed water at 37°C. The average lesion volume was measured by visible change in optical opacity and by T2-weighted magnetic resonance imaging. In addition, in vivo HIFU lesions were generated in a canine liver before and after an intravenous injection of droplets with a similar acoustic setup. Results Thermal lesions were sevenfold larger in phantoms containing droplets (3 × 10 5 droplets/mL) compared to phantoms without droplets. The mean lesion volume with a 2-second HIFU exposure in droplet-containing phantoms was comparable to that made by a 5-second exposure in phantoms without droplets. In the in vivo study, the average lesion volumes without and with droplets were 0.017 ± 0.006 cm 3 (n = 4; 5-second exposure) and 0.265 ± 0.005 cm 3 (n = 3; 5-second exposure), respectively, a factor of 15 difference. The shape of ADV bubbles imaged with B-mode ultrasound was very similar to the actual lesion shape as measured optically and by magnetic resonance imaging. Conclusion ADV bubbles may facilitate clinical HIFU ablation by reducing treatment time or requisite in situ total acoustic power and provide ultrasonic imaging feedback of the thermal therapy.