Phytophthora root and crown rot of safflower (Carthamus tinctorius) is regarded as one of the main soilborn diseases of this crop in Iran. Sampling and isolating of the causal agent was performed from farms in Ghazvin, Karaj and Isfahan. A frequently isolated oomycete called Phytophthora drechsleri was determined as the major pathogen of the disease. Twenty different genotypes of safflower were inoculated in mature and seedling stages using three different methods. Hypocotyls and cotyledons of 10-days seedlings were inoculated by putting a small disk of freshly prepared mycelial mat of pathogen. The results of two inoculation methods suggested that cultivars and lines including Gol sefid-e-Esfahan and KW10 in the hypocotyle method and local Ajabshir line in the second method of cotyledon inoculation had the highest level of tolerance to the pathogen. Results of detached leaf method indicated that the lines local Ajabshir, KW6, Golsefid Esfahan, Varamin295 and Zarghan279 have the highest level of tolerance to disease, respectively. The results suggest that local Iranian lines should have higher level of tolerance to the disease.