Two field experiments were conducted at the Research Farm, Agricultural Research Station, El-Kharga, New Valley Governorate, Egypt, during 2011/2012 and 2012/2013 seasons to study the impact of irrigation levels (I₁=100%, I₂= 80% and I₃= 60% of potential evapotranspiration, ET_p) and fertigation frequency (F₁= 3, F₂= 6, F₃= 12 and F₄= 18 doses) on safflower crop. The experiments were laid out in randomized complete block design in strip-plotarrangementwith three replicates. Results showed that the highest mean values of seed yield, oil yield and NPK use efficiency were recorded from drip irrigation at 100% of ET_p with number fertigation splitting to 12 equal doses. The increment percentage of seed yield due to I₁F₃ treatment over fertigation splitting 3 doses under the same irrigation treatment were 62.2% and 61.1%, 42.34% and 41.63% when using I₂F₄ treatment in both seasons, respectively as compared to 100% of ET_p with fertigation splitting 3 equal doses (I₁F₁). The highest mean values of water use efficiency were recorded from drip irrigation at 80% of ET_p with fertigation splitting 18 doses in both seasons. So, it is concluded that treated safflower plants with I₂F₄ to get economical yield and water use efficiency, respectively; therefore it may be saving 20% of irrigation water.