The molecular beam epitaxial growth and optimization of antimony-based interband cascade photodetectors, on both GaSb and GaAs substrates, are presented. Material characterization techniques, including X-ray diffraction, atomic force microscopy, and crosssectional transmission electron microscopy, are used to evaluate the epitaxial material quality. This work has led to the demonstration of mid-infrared photodetectors operational up to a record-high 450 K, and a dark current density as low as 1.10×10 -7 A/cm 2 at 150 K. The results also suggest that further improved material quality and device performance can be expected via optimization of growth parameters.