This article discusses the design and analysis of a portal imaging system based on a thick transparent scintillator. A theoretical analysis using Monte Carlo simulation was performed to calculate the x-ray quantum detection efficiency (QDE), signal to noise ratio (SNR) and the zero frequency detective quantum efficiency [DQE(0)] of the system. A prototype electronic portal imaging device (EPID) was built, using a 12.7 mm thick, 20.32 cm diameter, CsI(Tl) scintillator, coupled to a liquid nitrogen cooled CCD TV camera. The system geometry of the prototype EPID was optimized to achieve high spatial resolution. The experimental evaluation of the prototype EPID involved the determination of contrast resolution, depth of focus, light scatter and mirror glare. Images of humanoid and contrast detail phantoms were acquired using the prototype EPID and were compared with those obtained using conventional and high contrast portal film and a commercial EPID. A theoretical analysis was also carried out for a proposed full field of view system using a large area, thinned CCD camera and a 12.7 mm thick CsI(Tl) crystal. Results indicate that this proposed design could achieve DQE(0) levels up to 11%, due to its order of magnitude higher QDE compared to phosphor screen–metal plate based EPID designs, as well as significantly higher light collection compared to conventional TV camera based systems.