A large number of long-term field experiments demonstrate that optimal application of nitrogen fertilizers to crops did not result in loss of organic matter, nor did it adversely affect soil microbial activity. Optimal use of fertilizers on agricultural crops reduces soil erosion, but repeated application of high doses of nitrogen fertilizer can lead to soil acidification, a negative trait of soil health. The main objective of this paper is to study the particular effect, interaction and complementarity of NP, NPK and organo-mineral fertilizers on the production of agricultural crops. This paper presents production data as well as references that can be used to define the scientific bases of the multi-year application of fertilizers. The experimental technique is specific to the polyfactorial character and the analytical methods used are specific and current in the field. In this scientific paper, we present the results obtained for the cultivation of wheat and corn, during the period 2018-2023, at the "Mircea Motoc" Perieni Research-Development Station for Combating Soil Erosion, by fertilizing with several types of organo-mineral fertilizers. The results obtained come from the long-term experiences with fertilizers with 25 variants in the NP experience, respectively 16 variants in the NPK experience and the organo-mineral experience, all being placed according to the block method with parcels subdivided into 6 repetitions. The obtained results were interpreted by analysis of variance. From the results of this long-term experience, it is concluded that the effect of long-term fertilization with NP, NPK and organominerals responds to the maximization of profit and the optimization of the soil-plant system and environmental protection.