Developing ductile refractory alloys have remained a challenge. Decreasing the valence electron concentration of refractory alloys has been widely suggested for improving their ductility. However, Re has been used to ductilize W, which goes against the low valency suggestion. The thermodynamic stability of refractory alloys has never been considered while suggesting alloying elements to improve ductility. Here we use first-principles density functional theory simulations to unravel the role of enthalpy of formation in improving the intrinsic ductility of refractory alloys. The intrinsic ductility is assessed using the D-parameter, which is the ratio of surface energy and unstable stacking fault energy. We studied 25 equiatomic binary refractory alloys and found that positive enthalpy of formation improves ductility. The small positive enthalpy of formation could be compensated by sufficiently large entropy; hence the alloy is expected to be a single phase. Our present work explains the role of high-valency and low-valency alloying elements in improving the ductility of refractory alloys. These findings provide a path to design thermodynamically stable and intrinsically ductile high-temperature alloys.