The small thermal lesions induced when using high-intensity focused ultrasound (HIFU) to ablate tumors results in long treatment duration. In this study, the effect of using ultrasound contrast agent (UCA, Definity) to enhance the ultrasound (US) thermal effects and, thus to enlarge the lesion size, was studied in transparent tissue phantoms insonified by 1.85-MHz US with acoustical powers of 28.9 and 40.4 W. The experimental results show that the lesion size depended strongly on the electrical power and the concentration of UCA. UCA also reduced the power required to form a lesion of a certain size by about 30%. However, UCA moved the greatest heating position from the transducer focus, by 2.16 cm for 0.015% UCA at 40.4 W, and with lesions forming at the surface for UCA concentrations higher than 0.1%. An optimal result was obtained when using 0.001% UCA and 28.9-W US, which produced a lesion 12 times larger and an acceptable shift (less than half of the lesion length). UCA can effectively increase the size of the HIFU lesions, but lesion shift should be carefully considered while performing HIFU ablations.