A new method for portal dosimetry using CCD camera-based electronic portal imaging devices (CEPIDs) is demonstrated. Unlike previous approaches, it is not based on a priori assumptions concerning CEPID cross-talk characteristics. In this method, the nonsymmetrical and position-dependent cross-talk is determined by directly imaging a set of cross-talk kernels generated by small fields (“pencil beams”) exploiting the high signal-to-noise ratio of a cooled CCD camera. Signal calibration is achieved by imaging two reference fields. Next, portal dose images (PDIs) can be derived from electronic portal dose images (EPIs), in a fast forward-calculating iterative deconvolution. To test the accuracy of these EPI-based PDIs, a comparison is made to PDIs obtained by scanning diode measurements. The method proved accurate to within (1 SD), for on-axis symmetrical and asymmetrical fields with different field widths and homogeneous phantom thicknesses, off-axis Alderson thorax fields and a strongly modulated IMRT field. Hence, the proposed method allows for fast, accurate portal dosimetry. In addition, it is demonstrated that the CEPID cross-talk signal is not only induced by optical photon reflection and scatter within the CEPID structure, but also by high-energy back-scattered radiation from CEPID elements (mirror and housing) towards the fluorescent screen.