The management of fertilizer application is crucial for agricultural production and environmental safety. The objective of this study was to assess the effciency of different fertilization strategies, applying fertilizers with and without nitrification inhibitors (NIs) in split application, in Greece. The assessment criteria used were based on crop yield, soil nitrogen (N) concentrations and economic effciency. For this purpose two crops (winter wheat and cotton) were selected in order to explore the optimum fertilization strategy for each crop. Three treatments combining fertilizers with NIs were tested compared with conventional fertilization (CF). Slight differences in the quantity and the combination of fertilizers with NIs applied resulted in variable effects on crop yield, soil N and economic return. Split N application of 102 kg ha-1, with half of the total amount applied at seeding, resulted in higher grain yield of winter wheat, lower NO3-N in soil and higher economic return. This result reveals the importance of N application at seeding in wheat crop. Fertilization strategy with 109.5 kg N ha-1 and split P application resulted in higher cotton yield and higher economic profit. Split P application seemed to increase yield, even though it is not a common practise in the area. The management of fertilizer application is crucial for agricultural production and environmental safety. The objective of this study was to assess the effciency of different fertilization strategies, applying fertilizers with and without nitrification inhibitors (NIs) in split application, in Greece. The assessment criteria used were based on crop yield, soil nitrogen (N) concentrations and economic effciency. For this purpose two crops (winter wheat and cotton) were selected in order to explore the optimum fertilization strategy for each crop. Three treatments combining fertilizers with NIs were tested with conventional fertilization (CF). Slight differences in the quantity and the combination of fertilizers with NIs applied resulted in variable effects on crop yield, soil N and economic return. Split N application of 102 kg ha-1, with half of the total amount applied at seeding, resulted in higher grain yield of winter wheat, lower NO3-N in soil and higher economic return. This result reveals the importance of N application at seeding in wheat crop. Fertilization strategy with 109.5 kg N ha-1 and split P application resulted in higher cotton yield and higher economic profit. Split P application seemed to increase yield, even though it is not a common practice in the area.