High-intensity focused ultrasound (HIFU) therapy can be used for noninvasive treatment of kidney (renal) cancer, but the clinical outcomes have been variable. In this study, the efficacy of renal HIFU therapy was studied using nonlinear acoustic and thermal simulations in three patients. The acoustic simulations were conducted with and without refraction in order to investigate its effect on the shape, size, and pressure distribution at the focus. The values for the attenuation, sound speed, perfusion, and thermal conductivity of the kidney were varied over the reported ranges to determine the effect of variability on heating. Furthermore, the phase aberration was studied in order to quantify the underlying phase shifts using a second-order polynomial function. The ultrasound field intensity was found to drop on average 11.1dB with refraction and 6.4dB without refraction. Reflection at tissue interfaces was found to result in a loss less than 0.1dB. Focal point splitting due to refraction significantly reduced the heating efficacy. Of all the tissue parameters, perfusion was found to affect the heating the most. Small changes in temperature were seen with varying attenuation and thermal conductivity, but no visible changes were present with sound speed variations. The aberration study revealed an underlying trend in the spatial distribution of the phase shifts. The results show that the efficacy of HIFU therapy in the kidney could be improved with aberration correction. A method is proposed by which patient specific pretreatment calculations could be used to overcome the aberration and therefore make ultrasound treatment possible.