To investigate the effect of a double-exposure dual-energy subtraction (DES) technique on the diagnostic performance of radiologists detecting small pulmonary nodules on flat-panel detector (FPD) chest radiographs.Using FPD radiography 41 sets of chest radiographs were obtained from 26 patients with pulmonary nodules measuring ≤20mm and from 15 normal participants. Each dataset included standard and corresponding DES images. There were six non-solid, 10 part-solid, and 10 solid nodules. The mean size of the 26 nodules was 15±4.8mm. Receiver operating characteristic (ROC) analysis was performed to compare the performance of the eight board-certified radiologists.For the eight radiologists, the mean value of the area under the ROC curve (AUC) without and with DES images was 0.62±0.05 and 0.68±0.05, respectively; the difference was statistically significant (p=0.02). For part-solid nodules, the difference of the mean AUC value was statistically significant (AUC=0.61±0.07 versus 0.69±0.05; p<0.01); for non-solid nodules it was not (AUC=0.62±0.1 versus 0.61±0.09; p=0.73), and for solid nodules it was not (AUC=0.75±0.1 versus 0.78±0.08; p=0.23). For nodules with overlapping bone shadows, the difference of the mean AUC value was statistically significant (p=0.03), for nodules without overlapping, it was not (p=0.26).Use of a double-exposure DES technique at FPD chest radiography significantly improved the diagnostic performance of radiologists to detect small pulmonary nodules.