This article describes a new computation-based approach for designing ductile Nb-Ti-Cr-Al solidsolution alloys. The proposed approach is based on computation of the surface energy and the Peierls-Nabarro (P-N) barrier energy as a function of alloy composition. The surface energy is used as a measure of the resistance to cleavage fracture, while the P-N barrier energy is used as a measure of dislocation mobility. The ratio of the surface energy to the P-N barrier energy is utilized as a material index which can be adjusted by alloying additions. Analytical relations are developed for computing (1) the elastic constants in terms of the d ϩ s electrons per atom in the alloys and (2) the lattice parameter, surface energy, and P-N barrier energy in terms of alloy composition. Design of a ductile solid-solution alloy is achieved by manipulating the number of d ϩ s electrons, through alloying additions, to obtain a high value of the ratio of the surface energy to P-N barrier energy by reducing the misfit energy of the dislocation core. Applications of the methodology to designing binary, ternary, and quaternary Nb-based solid-solution alloys with Ti, Cr, and Al alloying additions are illustrated with promising results, demonstrating that the proposed methodology is a viable approach for alloy design.