AIMS: To measure the difference in cumulative doses received by the bladder (target) and integral doses with different clinical target volume (CTV) to planning target volume (PTV) margins, comparing set-up to skin tattoos versus image-guided radiotherapy to bone or soft tissue. MATERIALS AND METHODS: Four plans were generated on each planning computed tomography dataset using the CTV with 5, 10, 15, 20 mm PTV margins using a three-dimensional conformal four-field technique. Set-up data based on skin, bone and soft tissue to the bladder on pre-treatment cone beam computed tomography (CBCT) were recorded. In total, 316 CBCTs were evaluable from 10 bladder cancer patients. Each CBCT was fused to the planning computed tomography dataset using the isocentre corresponding to each of the three pre-treatment matching conditions. The target was contoured on each CBCT and called the CTV of the day and the plan was re-calculated to determine the dose to this. RESULTS: The mean D95 with CTV to PTV margins of 5, 10, 15 and 20 mm for skin set-up was 89.4, 93.0, 97.2, 98.6; for bone 88.8, 92.6, 96.7, 98.6; and for soft tissue 96.3, 98.6, 98.7, 99.5. With soft-tissue matching, the mean (standard deviation) volume of normal tissue receiving 5 Gy with 5, 10, 15 and 20 mm margins was 3899 (1022), 4561 (1142), 5663 (1304) and 6315 (1426) in cm(3). CONCLUSION: Soft-tissue matching results in superior target coverage and a reduced integral dose to the surrounding tissues. With soft-tissue matching, increasing CTV to PTV margins progressively beyond 5 mm results in modest improvement in CTV coverage, but a large increase in integral dose.