Purpose The use of volumetric modulated arc therapy (VMAT), simultaneous integrated boost (SIB), and hypofractionated regimen requires adequate patient setup accuracy to achieve an optimal outcome. The purpose of this study was to assess the setup accuracy of patients receiving left‐sided breast cancer radiotherapy using deep inspiration breath‐hold technique (DIBH) and surface guided radiotherapy (SGRT) and to calculate the corresponding setup margins. Methods The patient setup accuracy between and within radiotherapy fractions was measured by comparing the 6DOF shifts made by the SGRT system AlignRT with the shifts made by kV‐CBCT. Three hundred and three radiotherapy fractions of 23 left‐sided breast cancer patients using DIBH and SGRT were used for the analysis. All patients received pre‐treatment DIBH training and visual feedback during DIBH. An analysis of variance (ANOVA) was used to test patient setup differences for statistical significance. The corresponding setup margins were calculated using the van Herk's formula. Results The intrafractional patient setup accuracy was significantly better than the interfractional setup accuracy (p < 0.001). The setup margin for the combined inter‐ and intrafractional setup error was 4, 6, and 4 mm in the lateral, longitudinal, and vertical directions if based on SGRT alone. The intrafractional error contributed ≤1 mm to the calculated setup margins. Conclusion With SGRT, excellent intrafractional and acceptable interfractional patient setup accuracy can be achieved for the radiotherapy of left‐sided breast cancer using DIBH and modern radiation techniques. This allows for reducing the frequency of kV‐CBCTs, thereby saving treatment time and radiation exposure.