Federal law mandates that every checked bag at all commercial airports be screened by explosive detection systems (EDS), explosive trace detection systems (ETD), or alternative technologies. These technologies serve as critical components of airport security systems that strive to reduce security risks at both national and global levels. To improve the operational efficiency and airport security, emerging image-based technologies have been developed, such as dual-energy X-ray (DX), backscatter X-ray (BX), and multiview tomography (MVT). These technologies differ widely in purchasing cost, maintenance cost, operating cost, processing rate, and accuracy. Based on a mathematical framework that takes into account all these factors, this article investigates two critical issues for operating screening devices: setting specifications for continuous security responses by different technologies; and selecting technology or combination of technologies for efficient 100% baggage screening. For continuous security responses, specifications or thresholds are used for classifying threat items from nonthreat items. By investigating the setting of specifications on system security responses, this article assesses the risk and cost effectiveness of various technologies for both single-device and two-device systems. The findings provide the best selection of image-based technologies for both single-device and two-device systems. Our study suggests that two-device systems outperform single-device systems in terms of both cost effectiveness and accuracy. The model can be readily extended to evaluate risk and cost effectiveness of multiple-device systems for airport checked-baggage security screening.