[en] Purpose: To evaluate the role of cone-beam CT (CBCT) guidance for setup error reduction and soft tissue visualization in accelerated partial breast irradiation (APBI). Methods and Materials: Twenty patients were recruited for the delivery of radiotherapy to the postoperative cavity (3850 cGy in 10 fractions over 5 days) using an APBI technique. Cone-beam CT data sets were acquired after an initial skin-mark setup and before treatment delivery. These were registered online using the ipsilateral lung and external contours. Corrections were executed for translations exceeding 3 mm. The random and systematic errors associated with setup using skin-marks and setup using CBCT guidance were calculated and compared. Results: A total of 315 CBCT data sets were analyzed. The systematic errors for the skin-mark setup were 2.7, 1.7, and 2.4 mm in the right-left, anterior-posterior, and superior-inferior directions, respectively. These were reduced to 0.8, 0.7, and 0.8 mm when CBCT guidance was used. The random errors were reduced from 2.4, 2.2, and 2.9 mm for skin-marks to 1.5, 1.5, and 1.6 mm for CBCT guidance in the right-left, anterior-posterior, and superior-inferior directions, respectively. Conclusion: A skin-mark setup for APBI patients is sufficient for current planning target volume margins for the population of patients studied here. Online CBCT guidance minimizes the occurrence of large random deviations, which may have a greater impact for the accelerated fractionation schedule used in APBI. It is also likely to permit a reduction in planning target volume margins and provide skin-line visualization and dosimetric evaluation of cardiac and lung volumes