Drought stress is one of the most limiting factors in agricultural productivity because of its highly negative effect on photosynthesis and growth of plants. The main objectives of this study were to determine the performance of four selected safflower genotypes (Remzibey, Dinçer, Balcı and TRE-ASL09/14) against drought stress. The relationship between water use efficiency (WUE) and δ13C (isotope discrimination) was investigated under well watered (60%) and drought stress (30%) irrigation in controlled conditions in a green house. The result showed that drought stress clearly reduced plant biomass, leaf area, leaf number, relative water content (RWC), specific leaf weight (SLW), WUE and δ13C in all genotypes, while chlorophyll increased under drought stress. There were significant differences between performances of all safflower genotypes in terms of response to drought stress. High WUE and low δ13C discrimination under drought stress were inversely associated with a strong regression relationship (R2=0.75). The analysis of δ13C revealed a substantial variation in water use efficiency among the genotypes under drought stress. It was revealed that low δ13C discrimination types had high WUE, RWC and total biomass under drought stress. Thus, the ability of the low δC genotypes (high water use efficiency, WUE) to maintain higher RWC may provide a good indication of the differences in drought tolerance of safflower genotypes differing in δ13C. Overall, on the basis of the consistent percentage reductions in plant heights, total dry weight, leaf area, RWC, WUE and low δ13C, the TRE-ASL09/14 new breeding line was found to be more drought tolerant when compared with the other safflower hybrids under drought stress. As a result of our study it is suggested that there is a strong relationship between WUE and lower δ13C under drought stress, indicating that it may be used as a selection criterion for developing safflower genotypes with drought tolerance