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Improper nitrogen application time during the crop growing period is one of the most limiting factor for wheat production. A field experiment was conducted in Northwestern Ethiopia with the objective of determining the appropriate N fertilizer application time for improving bread wheat production. Twelve treatments (½ urea at 50% emergence + ½ urea at tillering, ½ urea at tillering + ½ urea at booting, 1/3rd urea at 50% emergence + 1/3rd urea at tillering + 1/3rd urea at booting, 2/3rd urea at tillering + 1/3rd urea at booting, all urea at tillering, all urea at booting, all N at tillering, all N at booting, ½ N at sowing+ ½ N at tillering, ½ N 50% emergence + ½ N at tillering, 1/3rd N at 50% emergence + 1/3rd N at tillering + 1/3rd N at booting, ½ N at tillering + ½ N at booting) were lied out in randomized complete block design (RCBD) with three replications. The study showed that wheat grain yield and protein content was highly influenced by the environment and indirectly correlated with each other as affected by N time of applications. The grain yield at Adet, Wonberema and Debre Elies was increased by 31%, 14% and 18%, respectively when N was applied with DAP at sowing over the blanket recommendation. At all locations, grain protein content decreased as the number of N split application increased 1 to 3 times. Thus, depending on the purpose of the producers, it can be concluded that application of ½ urea at 50% emergence + ½ urea at tillering with the application of DAP at sowing gave maximum wheat grain yield, while optimum grain protein content was obtained when N was applied after the crop is emerged and would be used in most dominant wheat producing areas of northwestern Ethiopia. Further study should be conducted on split application of blended fertilizers (NPS, NPSBZN etc.)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Derebe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)