During the past decade European wheat ( Triticum aestivum L.) crops were increasingly affected by Fusarium head blight (FHB) infection and high deoxynivalenol (DON) concentration in the grain. This is discussed to be primarily caused by the application of conservation tillage practices and, simultaneously, enhanced cultivation of host crops such as maize and wheat. This study investigated the effect of several environmental and management factors on DON formation and, particularly, interactions between factors. Moreover, a methodology was developed to quantify the relative effect of single factors, and combinations of two or more management factors on the DON concentration in order to evaluate management strategies with regard to their potential effect on DON formation. In 2001 and 2002, FHB infection of wheat and DON concentration in the grain was determined on eight sites of a long-term on-farm tillage experiment located in southern and eastern Germany. In addition, three-factorial plot trials varying tillage, cultivar, and fungicide application were conducted at Goettingen, Lower Saxony, in 2001 and 2002. Based on these data, the severity of the effect of year, preceding crop, tillage, wheat cultivar and fungicide application was calculated as follows: mean DON value of the treatment with the highest DON concentration obtained in the study divided by the lowest treatment mean value. For each influencing factor the calculation was done on average of the other factors included. The following ranking order was obtained: annual variation of rainfall during wheat anthesis (4.4) = Fusarium infection/susceptibility of the preceding crop (wheat versus sugar beet, 4.3) = Fusarium susceptibility of the wheat cultivar grown (4.3–5.6) > soil tillage applied to cultivate wheat (1.3–3.4) ≥ fungicide application at anthesis of wheat (2.1). The relative effect of combinations of two or more management factors on the DON concentration can be calculated by multiplying severity factors. Limitations of this method are due to strong interactions between some of the factors (e.g. cultivar × fungicide application, cultivar × tillage). Within tillage treatments shallow mixing conservation tillage increased the DON concentration only slightly compared to conventional mouldboard ploughing, if previous wheat straw soil cover was reduced to about 30%. In this case, the severity of the effect of tillage was much smaller compared to year, preceding crop, and cultivar. Data also reveal that FHB infection values counted in the field do not give a reliable prediction of the DON concentration. It is concluded, that choosing a resistant cultivar is a powerful tool to ensure a low DON concentration in wheat grain even under highly infectious conditions. This strategy enables farmers to make use of the benefits of conservation tillage and, simultaneously, produce high quality wheat grain.