By combining the cryo-EM and low dose data collection protocols implemented in EPU-D, the accumulated electron dose for each 3D ED dataset was below 1 e-/Å 2 in a 300kV electron microscope, which is approximately 3.8 MGy per crystal. No visible evidence of beam damage was observed in the reconstructed 3D reciprocal lattice. The protocol reported in this work is applicable to most organic small molecule crystals and macromolecule crystals.