Purpose We quantified prostate swelling and the intraprostatic point shift during high intensity focused ultrasound using real-time ultrasound. Materials and Methods The institutional review board approved this retrospective study. Whole gland high intensity focused ultrasound was done in 44 patients with clinically localized prostate cancer. Three high intensity focused ultrasound sessions were required to cover the entire prostate, including the anterior zone (session 1), middle zone (session 2) and posterior zone (session 3). Computer assisted 3-dimensional reconstructions based on 3 mm step-section images of intraoperative transrectal ultrasound were compared before and after each session. Results Most prostate swelling and intraprostatic point shifts occurred during session 1. The median percent volume increase was 18% for the transition zone, 9% for the peripheral zone and 13% for the entire prostate. The volume percent increase in the transition zone (p <0.001), peripheral zone (p = 0.001) and entire prostate (p = 0.001) statistically depended on the volume of each area measured preoperatively. The median 3-dimensional intraprostatic shift was 3.7 mm (range 0.9 to 13) in the transition zone and 5.5 mm (range 0.2 to 14) in the peripheral zone. A significant negative linear correlation was found between the preoperative presumed circle area ratio, and the percent increase in prostate volume (p = 0.001) and shift (p = 0.01) during high intensity focused ultrasound. Conclusions We quantified significant prostate swelling and shift during high intensity focused ultrasound. Smaller prostates and a smaller preoperative presumed circle area ratio were associated with greater prostate swelling and intraprostatic shifts. Real-time intraoperative adjustment of the treatment plan impacts the achievement of precise targeting during high intensity focused ultrasound, especially in prostates with a smaller volume and/or a smaller preoperative presumed circle area ratio.