For durum wheat, we promote the use of carbon isotope discrimination (delta) as an indirect selection criterion for transpiration efficiency and grain yield (GY), and we identify the most effective organ for characterising delta genotypic variation. A field experiment was conducted in the South of France on 144 accessions, with a drought period occurring from February to June. Harvest index (HI), GY and delta (delta L, flag leaf; delta A, awn, delta G grain) were measured. Significant positive genetic correlations were noted between delta and both GY and HI. A larger genotypic variation and a higher broad-sense heritability were noted for delta G compared to delta L and delta A. delta G correlated better with GY and HI than delta L and delta A, showing that delta G could provide a better assessment of genotypic behaviours under drought during grain filling. Moreover, the indirect selection based on delta G (even when evaluated with one replicate) appeared more efficient than the direct selection for grain yield. This result emphasised the potential value of grain carbon isotope discrimination as a criterion for grain yield improvement under stressed Mediterranean conditions.