Abstract: Radiotherapy quality assurance (QA) systems and methods are provided that incorporate a shared frame of reference between a treatment plan and a measured dose distribution that allows for 3D dosimetry measurements. An on-board imaging system may provide a shared frame of reference with the radiotherapy treatment system. A dosimeter is also provided for use with the QA systems and methods. The QA systems and methods can be applied as an end-to-end test to evaluate specific parameters of a radiation therapy treatment system, such as an external beam radiotherapy system, including spatial accuracy, isocenter verification and dosimetric accuracy.