Purpose High–dose rate brachytherapy (HDRB) is frequently used as a boost to external beam radiation therapy (EBRT) in prostate cancer patients. With the increasing use of small planning target volume margins in EBRT, prostatic edema induced by HDRB can be a contributing factor to geometric miss when HDRB is performed before or during EBRT. We assessed prostate gland volumetric change after single-fraction HDRB and its impact on definition of treatment volume for EBRT. Methods and Materials Thirty-one consecutive patients with intermediate-risk prostate cancer treated with single-fraction HDRB (10 Gy) combined with hypofractionated EBRT were analyzed. A second CT scan was performed 7 days after HDRB, and images were coregistered with the planning CT scan that contained the original clinical target volume (CTV). The post-HDRB prostate CTV volume was compared with the original CTV by a single observer. Results All patients presented volumetric variation. In most cases (68%), the prostate increased in volume, whereas it decreased in 32%. The mean prostatic volume was 42.2 cc before HDRB and 43.6 cc after HDRB, representing a mean volume difference of 3.4%, ranging from −14.2% to 23.8% ( p = 0.756). This difference is the result of mean changes of 0.6 mm (−6.1 to 6.6) in the anterior–posterior, 0.5 mm (−5.5 to 3.0) in the lateral, and 0.2 mm (−5.0 to 5.0) in the superior–inferior axes. Conclusions Although a nonsignificant volumetric change occurs after single-fraction HDRB, individual variations on specific axis could lead to important uncertainties during EBRT.