Purpose: To determine whether image guidance can improve the dose delivered to target organs and organs at risk (OARs) for prostate cancer patients treated with intensity-modulated radiotherapy (IMRT). Methods and Materials: Eight prostate cancer patients were treated with IMRT to 76 Gy at 2 Gy per fraction. Daily target localization was performed via alignment of three intraprostatic fiducials and weekly kV-cone beam computed tomography (CBCT) scans. The prostate and OARs were manually contoured on each CBCT by a single physician. Daily patient setup shifts were obtained by comparing alignment of skin tattoos with the treatment position based on fiducials. Treatment fields were retrospectively applied to CBCT scans. The dose distributions were calculated using actual treatment plans (an 8-mm PTV margin everywhere except for 6-mm posteriorly) with and without image guidance shifts. Furthermore, the feasibility of margin reduction was evaluated by reducing planning margins to 4 mm everywhere except for 3 mm posteriorly. Results: For the eight treatment plans on the 56 CBCT scans, the average doses to 98% of the prostate (D98) were 102% (range, 99-104%) and 99% (range, 45-104%) with and without image guidance, respectively. Using margin reduction, the average D98s were 100% (range, 84-104%) and 92% (range, 40-104%) with and without image guidance, respectively. Conclusions: Currently, margins used in IMRT plans are adequate to deliver a dose to the prostate with conventional patient positioning using skin tattoos or bony anatomy. The use of image guidance may facilitate significant reduction of planning margins. Future studies to assess the efficacy of decreasing margins and improvement of treatment-related toxicities are warranted. © 2010 Elsevier Inc. All rights reserved.