This study was conducted on the Experimental Farm of the Shandaweel Research Station at Sohage, Egypt, during 2006/07 and 2007/08 growing seasons. The investigation was aimed to study the effect of irrigation at 45, 60 and 75% of available soil water deficit (ASMD) and two plant population densities (35000 and 70000 plants/ fad.) on productivity and water use efficiency of some genotypes (Lines 1, 2, 3 and Giza1 cv) of safflower. A randomized complete block, split-split plot design with three replicates was used in each season. Irrigation treatments, genotypes and plant population densities were randomly assigned to the main, sub-plots and subsub plots, respectively. Results showed that irrigation at 45% of ASMD significantly increased plant height, number of branches /plant, number of heads /plant, 100-seed weight, weight of seeds /plant, seed yield /fad., seed oil content and oil yield /fad. by 35.0, 45.8, 50.6 13.9, 49.9, 34.0, 7.3 and 43.8%, respectively, compared to irrigation at 75% of ASMD. Increasing plant population densities from 35000 to 70000 plants /fad. significantly increased plant height, seed and oil yield fad-1 , while, decreased number of branches /plant, number of heads /plant, 100-seed weight, weight of seeds /plant. In this case, seed oil content was not affected by plant population density. In general, Line 3 surpassed others genotypes in the most studied characteristics. The interaction between irrigation regime x genotype as well as irrigation regime x plant population density had a significant effect on the 100-seed weight, seed weight /plant, seed yield /fad., seed oil content, oil yield /fad and WUE. Meanwhile, interaction between plant population density x genotype or between three factors, had a significant effect on seed yield /fad. and WUE only. Seasonal water consumptive use was 30.03, 26.05 and 23.95 cm when irrigated safflower plants at 45%, 60% and 75% of ASMD, respectively. Results indicated that irrigation at 60% of ASMD gave the highest value of WUE (31.32 kg seed yield cm-1 of water consumed). Also, plant population densities at 70000 plants /fad. gave the highest value of WUE. Moreover, Line 3 was more efficient in water use than other genotypes. So, from results of seed yield and WUE, a high or medium irrigation rates with high plant population densities and planted safflower genotype Line 3 are adequate under this study condition.