Drought stress as the most important abiotic stress plays an important role in yield of plants worldwide. This study was conducted to evaluate drought tolerance of 100 safflower genotypes (Carthamus tinctorius L.) based on morphological, physiological and seed production traits at Research Farm of Isfahan University of Technology during 2012. Genotypes were evaluated under moisture stress and non-stress according to a simple lattice design with two replications. Result of analysis of variance showed that genotypes varied significantly for all the studied traits indicating high level of variation in the studied germplasem. Results showed that drought stress significantly affected day to maturity, seed yield per plant, plant height, branching height, number of heads per plant, oil percent, harvest index, biological yield, proline, RWC, chlorophyll a contact and chlorophyll a+b . The highest broad sense heritability in both moisture conditions (non-stress and drought stress) was belonged to plant height (87 and 92 percent, respectively) and the lowest one was estimated for biological yield (10 and 38 percent, respectively). High broad sense heritability and low difference were observed between genetic and phenotypic coefficients of variation for most of the traits. Genetic and phenotypic correlation coefficients in two moisture conditions showed that number of branches per plant, number of heads per plant, number of seeds per head and thousand seed weight had positive and significant correlation with seed yield. Between physiological traits chlorophyll a, chlorophyll b and carotenoid content had positive and high correlation with seed yield under stress condition. The results of factor analysis indicated 5 and 3 factors explaining 74% and 63% of total variation of yields under normal and stress conditions, respectively. The results of stepwise regression showed that number of head per plant, number of seed per head and thousand seed weight contributed in 89% of the observed variation for seed yield under normal condition. Under stress environment the traits number of head per plant, number of seed per head, thousand seed weight and plant height contributed in 82% of the observed variation for seed yield. Path coefficient analysis showed that the number of seed per head had the most direct effect on seed yield under both moisture environments. Analysis of variance for drought tolerance and susceptibility indices based on seed yield under stress and non-stress conditions showed that there were significant differences among drought tolerance indices indicating that these indices can be useful for selection of tolerant genotypes. Among the calculated indices stress tolerance index (STI) and geometric mean productivity (GMP) were identified as the superior indices for selection of drought tolerant genotypes under field condition. Aaccording to the results of present study, it is concluded that the genotype PI 369847 (from Tajikestan) and CART 56 (from USA) had high seed yield and more drought tolerance which can be used for future breeding programs to develop superior varieties for arid region.