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Sorghum [Sorghum bicolor (L.) Moench] is a C4 cereal grain crop grown primarily in arid and semi-arid regions in the world with limited or no irrigation. Sorghum production fluctuates and largely depends on the amount and distribution of rainfall. Transpiration efficiency (TE), the biomass produced per unit water transpired, could be a potential trait to improve sorghum yield in areas where irrigation is limited. We have developed a mini-lysimetric method that directly measures whole plant TE in sorghum during an early vegetative stage under greenhouse conditions. The method was evaluated with 11 inbred lines and three hybrids under two greenhouse environments. In general, TE determined with the gravimetric method was higher under lower vapor pressure deficit conditions; however, similar rankings in TE were obtained across the experiments. The method described in this report offers a simple, high-throughput, and affordable way to determine the integrated TE in sorghum at an early vegetative stage.