This paper applied an extended total factor productivity analysis to compare the resource use efficiency of alternative cropping systems in eastern Ethiopia. The results indicated considerable variation in resource use efficiency among cropping systems. Intercropping of sorghum with pulses in the dry lands and intercropping of maize with potatoes in the wet highlands turned out to be the most efficient practices. The results have important implications for research and extension services not only for promoting innovative cropping systems but also for integrating currently available improved technologies into the complex farming systems that are dictated by agro-climatic and demographic factors.