For three-dimensional (3D) structure determination of large macromolecular complexes, single-particle electron cryomicroscopy is considered the method of choice. Within this Weld, structure determination de novo, as opposed to reWnement of known structures, still presents a major challenge, especially for macromolecules without point-group symmetry. This is primarily because of technical issues: one of these is poor image contrast, and another is the often low particle concentration and sample heterogeneity imposed by the practical limits of biochemical puriWcation. In this work, we tested a state-of-the art 4k £ 4k charge-coupled device (CCD) detector (TVIPS TemCam-F415) to see whether or not it can contribute to improving the image features that are especially important for structure determination de novo. The present study is therefore focused on a comparison of Wlm and CCD detector in the acquisition of images in the low-to-medium (»10-25 Å) resolution range using a 200 kV electron microscope equipped with Weld emission gun. For comparison, biological specimens and radiation-insensitive carbon layers were imaged under various conditions to test the image phase transmission, spatial signal-to-noise ratio, visual image quality and power-spectral signal decay for the complete imageprocessing chain. At all settings of the camera, the phase transmission and spectral signal-to-noise ratio were signiWcantly better on CCD than on Wlm in the low-to-medium resolution range. Thus, the number of particle images needed for initial structure determination is reduced and the overall quality of the initial computed 3D models is improved. However, at high resolution, Wlm is still signiWcantly better than the CCD camera: without binning of the CCD camera and at a magniWcation of 70k£, Wlm is better beyond 21 Å resolution. With 4-fold binning of the CCD camera and at very high magniWcation (>300k£) Wlm is still superior beyond 7 Å resolution.