This work presents an approach to the fast determination of a medical accelerator irradiation isocenter as a quality assurance (QA) procedure in radiotherapy. The isocenter determination tool is the tissue equivalent high-resolution 3D polymer gel dosimeter (PABIGnx) in a dedicated container combined with kilovoltage imaging systems and the polyGeVero-CT software package (v. 1.2, GeVero Co., Poland). Two accelerators were employed: Halcyon and TrueBeam (Varian, USA), both equipped with cone beam computed tomography (CBCT) and iterative reconstruction CBCT (iCBCT) algorithms. The scope of this work includes: (i) the examination of factors influencing image quality (reconstruction algorithms and modes), radiation field parameters (dose and multi-leaf collimator (MLC) gaps), fiducial markers, signal averaging for reconstruction algorithms and the scanning time interval between consecutive scans, (ii) the examination of factors influencing the isocenter determination, image processing (signal averaging, background subtraction, image filtering) and (iii) an isocenter determination report using a 2D and 3D approach. An optimized protocol and isocenter determination conditions were found. The time and effort required to determine the isocenter are discussed.