An alumina (Al2O3) diffusion barrier coating to inhibit the interfacial reactions between boron-carbide-coated boron (B4C/B) fibers and a nickel-aluminide (Ni3Al) (IC-221) matrix was investigated. The alumina diffusion barrier was deposited on the B4C/B fibers using chemical vapor deposition. Also, Saphikon single-crystal Al2O3 fibers were used to demonstrate the compatibility between Al2O3 and Ni3Al. The detailed microstructures and chemical compositions of the fibers, coating, and matrix before and after various thermal exposures were analyzed using scanning electron microscopy, energy dispersive x-ray analysis, and ion microprobe mass analysis. The interfacial reaction products present after 6 h at 980 °C were characterized, and Ni was found to be the dominant diffusion species. The alumina diffusion barrier shows promise for effectively inhibiting the deleterious reactions between B4C/B fibers and the Ni3Al matrix. The uncoated B4C/B fibers were consumed by the matrix after fabrication alone, whereas the Al2O3 coated fibers demonstrated resistance to the matrix for 25 h at 880 °C and 6 h at 980 °C. The Saphikon fiber-reinforced Ni3Al composites demonstrated excellent compatibility after 50 h at 1000 °C. Zirconium (Zr)-rich precipitates on the order of 2 μm in diameter formed at the fiber interface after this exposure, but no gross reaction was indicated between the fiber and the matrix.