The new ORCA-Flash4.0 scientific CMOS camera features good quantum efficiency, low noise, and better signal-to-noise characteristics. The camera covers a range of imaging needs including super resolution microscopy, TIRF microscopy, live-cell GFP, high-speed calcium ion imaging, FRET, and real-time confocal microscopy. The ORCA-Flash4.0 has quantum efficiency values of over 70% at 600 nm and 50% at 750 nm, and has only 1.3 electrons of read noise (at 100 full-resolution frames per second). With 4.0 megapixels at 6.5 μm × 6.5 μm each, the ORCA-Flash4.0 is formatted for demanding microscopy applications.