PurposeThis study uses a phantom to investigate the dosimetric impact of rotational setup errors for Single Isocenter Multiple Targets (SIMT) HyperArc plans. Additionally, it evaluates intra‐fractional rotational setup errors in patients treated with Encompass immobilization system.MethodsThe Varian HyperArc system (Varian Medical systems) was used to create plans targeting spherical PTVs with diameters of 5, 10, and 15 mm and with offsets of 1.3–5.3 cm from the isocenter. Dosimetric parameters, including mean and maximum dose, D99% and D95% were evaluated for various rotational setup errors ranging from 0.5° to 2° for the PTVs and certain CTVs created within PTVs. These rotational errors were applied in an order and direction that resulted in the maximum displacement of targets. The rotation was applied both uniformly around all three axes and individually around each axis. Furthermore, to link the findings to actual treatment scenarios, the intra‐fractional rotational setup errors were obtained for stereotactic cranial patients treated with the Encompass system using CBCT images acquired during treatments.ResultsThe maximum displacement of 2.7 mm was observed for targets located at 4.4 and 4.5 cm from the isocenter with rotational setup errors of 2°. The dose reduction for D99% values corresponding to this displacement were about 50%, 40%, and 30% for PTVs with diameters of 5, 10, and 15 mm, respectively. Both D99% and D95% showed a consistent trend of dose reduction across various rotational errors and PTV volumes. While the maximum dose remained consistent for different targets with various rotational errors, the mean dose decreased by approximately 25%, 12%, and 6% for PTVs with diameters of 5, 10, and 15 cm, respectively, with rotational errors of 2°. In addition, by analyzing CBCT images, the absolute mean rotational setup errors obtained during treatment with Encompass for pitch, roll, and yaw were 0.17° ± 0.13°, 0.11° ± 0.10°, and 0.12° ± 0.10° respectively. This data, combined with existing studies, suggest that a 0.5° rotational setup error is a safe choice to consider for calculating additional PTV margin to ensure adequate CTV coverage.Therefore, the assessment of maximum displacement and dosimetric parameters in this study, for a 0.5° rotational error, highlights the need for an additional 0.7 mm PTV margin for targets positioned at distances of 4.4 cm or greater from the isocenter.ConclusionsFor SIMT Plans, a 0.5° rotational setup error is recommended as a basis for calculating additional PTV margins to ensure adequate CTV coverage when using the Encompass system.