Background: In locoregional radiotherapy of breast cancer with deep inspiration breath hold (DIBH), setup accuracy may depend on hospital protocol. At present, comparison between different positioning devices is challenging due to differing hospital protocols. The aim of this study was to evaluate the setup accuracy obtained with surface-guided radiation therapy (SGRT; AlignRT®, Catalyst™) or with lasers and real-time position management (RPM™) in DIBH. Materials and methods: A total of 1692 image pairs were analyzed in three groups: positioning using AlignRT® surface guidance system (Group A, n = 45), Catalyst™ (Group C, n = 50) and conventional lasers and tattoos (Group L, n = 46). We evaluated residual errors for the bony chest wall, th1 and humeral head in kV images with laser or SGRT-based setup with and without daily image-guided radiation therapy (IGRT). Results: Less isocenter variance was found in Group A than in Group L or C (p ≤ 0.05) and in Group C than in L (p = 0.02–0.6). With SGRT only, the smallest random rotation error was found in Group A (p = 0.01). With daily IGRT, only a small difference was found for residual errors between the groups. Conclusion: Setup with SGRT improves the isocenter reproducibility compared to lasers and RPM™. Only small differences were found in setup accuracy between the SGRT devices. Due to improved isocenter accuracy, daily orthogonal IGRT is suggested in all the groups.