An experiment was conducted at the Agricultural Research Station of Isfahan University of Technology during summer 2010 in order to evaluate the effects of nitrogen application under different levels of irrigation on yield, yield components and fatty acids composition of safflower. Three nitrogen rates (0, 50 and 100 kg ha -1 ) at three levels of irrigation ( based on 60, 80 and 100% of crop water requirement ) were investigated using a randomized complete block design with a factorial laid out and four replications. Nitrogen application led to a significant increase in leaf chlorophyll content, photochemical efficiency, leaf relative water content, leaf proline content , number of branches per plant, leaf area index, shoot dry weight,, number of buttons per plant, number of grains per button, grain weight, grain yield, harvest index, oil yield and water use efficiency. There was no significant effect of nitrogen application on the grain oil percentage. Photochemical efficiency, leaf relative water content, number of branches per plant, leaf area index, shoot dry weight, number of buttons per plant, number of grains per button, grain weight, grain yield, oil percentage, oil yield and harvest index were decreased and leaf chlorophyll content, leaf proline content and water use efficiency were increased as the level of soil moisture was decreased. The concentration of oleic acid was increased and those of stearic and palmitic acid were decreased at high level of nitrogen application compared to control. Under irrigation regime based on 60% compared to irrigation regime based on 100% of crop water requirement, the concentrations of oleic and palmitic acid were increased and those of linoleic, stearic, and linolenic acid were decreased. The highest amount of grain yield (3263 kg ha -1 ) was obtained with application of 100 kg/ha nitrogen under irrigation regime of 100% crop water requirement and the lowest amount (1914 kg ha) was obtained with no nitrogen application under irrigation regime based on 60% crop water requirement . The highest value of harvest index was achieved with application of 100 kg/ha nitrogen under irrigation regime based on 100% crop water requirement and the highest water use efficiency was obtained with application of 100 kg/ha nitrogen under irrigation regime based on 60% crop water requirement. The results from this experiment showed that the effect of nitrogen application on yield and yield components of safflower is dependent on the level of soil moisture. Key Word safflower, nitrogen application, levels of irrigation, yield, yield components, fatty acids, water use effeciency