Wild relatives of safflower possess useful genes which could be incorporated into cultivated species using inter-specific hybridization. The current investigation was carried out in the form of two separate studies. The first study was performed to evaluate genetic diversity, drought tolerance and assessment of production potential of 140 families from eight F 3 populations obtained from direct and reciprocal crosses of three safflower species including C. tinctorious , C. palestinus and C. oxyacanthus. Two genotypes of cultivated safflower brifly “I” and “C” were crossed with C. palestinus (P) and C. oxyacanthus (O) in both directions. All F 3 families along with their parental lines were investigated in water stress and non-stress conditions according to a simple lattice design. The second study was performed to assess the inheritance of qualitative traits of 240 families of five F 3 populations obtained from the crosses of three safflower species including C. tinctorious , C. palestinus and C. oxyacanthus . According to the results of the first study, there was a significant difference among all the F 3 families as well as F 3 lines of different crosses for all the measure traits indicating a high variation in this germplasm. The highest genetic variation was observed for the yield traits at the non-stress condition and the number of capitula per plant at the drought stress condition. The phonotypic and genetic coefficient of variation and broad-sense heritability declined at drought stress condition for most of the traits measured. The drought stress caused a meaningful decrement in traits including, grain yield, the number of capitula per plant, plant height, the number of branches, the capitula diameter, the 100-grain weight, the number of grain per capitula and grain yield per capitula. The crosses obtained from wild species of C. palaestinus with cultivated species had more yield at both moisture conditions when compared to other crosses in respect to higher grain yield and its components. The CP and IP crosse had the highest heritability for the seed yield at the non-stress and drought stress conditions, respectively. According to the drought susceptibility indices (SSI, TOL) wild species of C. oxyacanthus as a parental line and among crosses OP had the lowest values. Based on the drought tolerance indices (MP, GMP and STI), wild species of C. palaestinus among the parents and PI, IP, CP and PC crosses had the highest tolerance which was confirmed by the bi-plot of principal components analysis. The stress tolerance (STI) and geometric mean productivity (GMP) indices were identified as the best indices for choosing the most tolerant crosses. In assessing the relation of the traits, the results of path analysis revealed that the number of capitulas per plant at the non-stress condition and the number of grain per capitula at the drought stress condition had the most direct effect on grain yield of safflower. Based on the results of the second study, for the having dentate of rosette leaf edge, Spininess, shape of bracket, shape of the seed, complete dominance gene action and for the Notch of rosette leaf and bracket size incomplete dominance gene action were observed. Keywords : Safflower, Wild relatives, Inter-specific Hybridization, Drought Stress, Inheritance