This paper investigates the clinical significance of real‐time monitoring of intrafractional prostate motion during external beam radiotherapy using a commercial 4D localization system. Intrafractional prostate motion was tracked during 8,660 treatment fractions for 236 patients. The following statistics were analyzed: 1) the percentage of fractions in which the prostate shifted 2−7 mm for a certain duration; 2) the proportion of the entire tracking time during which the prostate shifted 2−7 mm; and 3) the proportion of each minute in which the shift exceeded 2−7 mm. The ten patients exhibiting maximum intrafractional‐motion patterns were analyzed separately. Our results showed that the percentage of fractions in which the prostate shifted by >2,3,5,and 7 mm off the baseline in any direction for >30 normals was 56.8%, 27.2%, 4.6%, and 0.7% for intact prostate and 68.7%, 35.6%, 10.1%, and 1.8% for postprostatectomy patients, respectively. For the ten patients, these percentages were 91.3%, 72.4%, 36.3%, and 6%, respectively. The percentage of tracking time during which the prostate shifted >2,3,5,and 7 mm was 27.8%, 10.7%, 1.6%, and 0.3%, respectively, and it was 56.2%, 33.7%, 11.2%, and 2.1%, respectively, for the ten patients. The percentage of tracking time for a >3 mm posterior motion was four to five times higher than that in other directions. For treatments completed in 5 min (VMAT) and 10 min (IMRT), the proportion for the prostate to shift by >3 mm was 4% and 12%, respectively. Although intrafractional prostate motion was generally small, caution should be taken for patients who exhibit frequent large intrafractional motion. For those patients, adjustment of patient positioning may be necessary or a larger treatment margin may be used. After the initial alignment, the likelihood of prostate motion increases with time. Therefore, it is favorable to use advanced techniques (e.g., VMAT) that require less delivery time in order to reduce the treatment uncertainty resulting from intrafractional prostate motion.PACS number: 87.50.S‐, 87.53.Kn, 87.55.N‐, 87.55.ne