The purpose of this study was to evaluate the clinical utility of an investigational flat-panel digital radiography system for low-dose portable neonatal imaging. Thirty image-pairs from neonatal intensive care unit patients were acquired with a commercial Computed Radiography system (Agfa, ADC 70), and with the investigational system (Varian, Paxscan 2520) at one-quarter of the exposure. The images were evaluated for conspicuity and localization of the endings of ancillary catheters and tubes in two observer performance experiments with three pediatric radiologists and three neonatologists serving as observers. The results indicated no statistically significant difference in diagnostic quality between the images from the investigational system and from CR. Given the investigational system's superior resolution and noise characteristics, observer results suggest that the high detective quantum efficiency of flat-panel digital radiography systems can be utilized to decrease the radiation dose/exposure to neonatal patients, although post-processing of the images remains to be optimized. The rapid availability of flat-panel images in portable imaging was found to be an added advantage for timely clinical decision-making.