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pyXSIM simulates X-ray observations from astrophysical sources. X-rays probe the high-energy universe, from hot galaxy clusters to compact objects such as neutron stars and black holes and many interesting sources in between. pyXSIM generates synthetic X-ray observations of these sources from a wide variety of models, whether from grid-based simulation codes such as FLASH (ascl:1010.082), Enzo (ascl:1010.072), and Athena (ascl:1010.014), to particle-based codes such as Gadget (ascl:0003.001) and AREPO (ascl:1909.010), and even from datasets that have been created “by hand”, such as from NumPy arrays. pyXSIM can also manipulate the synthetic observations it produces in various ways and export the simulated X-ray events to other software packages to simulate the end products of specific X-ray observatories. pyXSIM is an implementation of the PHOX (ascl:1112.004) algorithm and was initially the photon_simulator analysis module in yt (ascl:1011.022); it is dependent on yt.