To investigate the effect of different levels of irrigation and nitrogen fertilizer on yield and yield components of some safflower cultivars, an experiment was conducted as a split-split plot in a randomized complete blocks design with three replications in the research farms of the University of Tehran, Karaj during 2018-2019. Main plots were irrigation (normal irrigation, irrigation until at middle of flowering stage and irrigation until the beginning of seed filling), sub plots were nitrogen (supply of 100% and 50% of nitrogen needs) and sub-sub plots were safflower cultivars (Goldasht, Golmehr, Padideh and Parnian). The effect of irrigation, nitrogen, and cultivar factors on diameter and number of heads per plant, number of seeds per head, 1000-seed weight, grain yield, and biomass were significant at the level of 1% probability. According to the results, cut-off of irrigation at the beginning of seed filling and middle of flowering stages leads to a reduction of 40.5% and 69.3% of seed yield compared to normal irrigation, respectively. Reducing the amount of nitrogen by 50% compared to 100% supply decreases seed yield 25.7% and biomass by 20.1%. The interaction of irrigation and nitrogen levels showed that providing 100% of nitrogen needs under drought stress prevents a severe decline in yield. As a result of the interaction of irrigation levels and cultivars in this experiment, Goldasht cultivar in head diameter trait and Parnian and Goldasht cultivars in the number of seeds per head and 1000-seed weight traits showed the superiority.