We previously developed an ultrasonic elastography imaging system that may provide a simple and cost-effective solution to monitor high-intensity focused ultrasound (HIFU) treatments. The objective of this clinical study was to evaluate the reliability of our system in assessing the volume of HIFU lesions in the prostate, using a comparison with magnetic resonance imaging (MRI). Elastograms were obtained in 20 patients after HIFU treatment for prostate cancer and gadolinium-enhanced T1- and T2-weighted MRI was performed. Lesion boundaries were manually outlined and the volume was calculated. A statistically significant correlation of rho = 0.62 (p = 0.022) was found between elastographic and MRI measurements of lesion volume, with elastographic measurements that generally underestimated the volume measured in MRI. Some basic physics (hypoechoic areas) and instrumentation (frame rate and band width) issues that were detrimental to image quality in vivo are reported, along with propositions to improve the technique. Because of these issues and, although good correspondence between elastographic and MRI measurements was found in some patients, elastographic measurements were unable to predict MRI measurements in a single individual. Nevertheless, the results confirmed the potential of elastography for monitoring HIFU treatment of the prostate. Further investigation will be conducted using better suited ultrasound equipment and performing real-time elastogram calculations.