Two field experiments were carried out during two successive winter seasons of 2010/2011 and 2011/2012 in the experimental farm, Agricultural Research Station of El-Kharga, the New Valley Government under sprinkler irrigation system to study the effect of three irrigation regimes (0.8, 1.0 and 1.2 IW:CPE), two wheat cultivars (Sakha-94 and Bani Suef-6) and four nitrogen fertilization treatments (100% inorganic-N, F₁; 70% inorganic-N+3 ton compost+ N-fixers, F₂; 70% inorganic-N +5 ton compost+ N-fixers, F₃; 70% inorganic-N+7ton compost+ N-fixers, F₄) on yield and its components, actual evapotransiration and water use efficiency of wheat. Results indicated that irrigated wheat plants with 1.2 IW: CPE increased biological, grain yields, ET_a and WUE by 11.48, 58.46, 27.35 and 24.27% as compared with 0.8 IW:CPE, respectively. The superiority of Bani Suef-6 wheat cultivar over Sakha-94 was confirmed for 1000-grain weight, biological, grain yields and WUE. Meanwhile, Sakha-94 cultivar gave the highest values of number of spikes per m², straw yield and ET_a compared to Bani Suef 6 cultivar. Raising compost level from 0 to 7 ton fed^-1 with applying N-fixers and decreasing inorganic N by 30% caused increasing 1000-grain weight, biological, grain yields, ET_a and WUE. In general, the followed interaction treatments were the best treatments because they gave highest grain yield and WUE: irrigated Bani Suef-6 plants with 1.2 IW:CPE+F₄; 1.2 IW:CPE+F₃ and 1.0 IW:CPE+F₄.