HgCdTe has been called the ideal infrared detector material for good reason: high absorption coefficients and very long Shockley-Read-Hall (SRH) recombination lifetimes lead to the highest performance infrared detectors today for space applications. III-V materials, such as InAsSb, are currently limited by short SRH recombination lifetimes due to defects, and their performance is still relatively lacking for space applications where sensitivity requirements are extremely high. However, the performance of III-V superlattice infrared detectors has improved such that it is sufficient for tactical applications, which can now take advantage of the manufacturing benefits of III-V (greater uniformity and yield). With the growing NewSpace movement, there is a need for higher-volume, lower-cost infrared detectors capable of operating in space for applications such as environmental monitoring, space-based weather, and planetary science. One way to increase volume and lower cost is to grow the detectors on large-format substrates, such as 6-inch silicon or GaAs, but lattice-matched large substrates are not available for HgCdTe or InAsSb. Here a comparison between mid-wavelength infrared HgCdTe and InAsSb infrared detectors grown on non-lattice-mismatched substrates and designed for increased proton radiation tolerance, as compared to previous designs on mismatched substrates, is given. The comparison of these recent HgCdTe photodiode and InAsSb bariode designs for space applications shows that the InAsSb bariode has an order of magnitude better dark current density proton radiation tolerance while the HgCdTe photodiode has an order of magnitude better quantum efficiency proton radiation tolerance operating at 130 K. Therefore, the choice of detector material and architecture is not clear and will depend on the required performance for a specific space application.