The accumulation of injected contrast agents allows the image enhancement of lesions through the use of contrast-enhanced mammography. In this technique, the combination of two acquired images is used to create an enhanced image. There exist several methods to acquire the images to be combined, which include dual energy subtraction using a single detection layer that suffers from motion artifacts due to patient motion between image acquisition. To mitigate motion artifacts, a detector composed of two layers may be used to simultaneously acquire the low and high energy images. In this work, we evaluate both of these methods using amorphous selenium as the detection material to find the system parameters (tube voltage, filtration, photoconductor thickness and relative intensity ratio) leading to the optimal performance. We then compare the performance of the two detectors under the variation of contrast agent concentration, tumor size and dose. The detectability was found to be most comparable at the lower end of the evaluated factors. The single-layer detector not only led to better contrast, due to its greater spectral separation capabilities, but also had lower quantum noise. The single-layer detector was found to have a greater detectability by a factor of 2.4 for a 2.5 mm radius tumor having a contrast agent concentration of 1.5 mg ml−1 in a 4.5 cm thick 50% glandular breast. The inclusion of motion artifacts in the comparison is part of ongoing research efforts.