Fusarium head blight (FHB), caused by Fusarium graminearum, is a major threat to food safety and security, because it reduces crop yields and contaminates grains with mycotoxins which negatively impact the health of both humans and livestock. Production of the mycotoxin deoxynivalenol (DON) is not required for initial F. graminearum infection of wheat heads but is essential for the spread of the fungus within wheat heads. Therefore, suppression of DON production is an attractive FHB control strategy. Endophytes, bacteria or fungi, form intrinsic relationships with their hosts and can inhabit host tissue without causing damage. Previous studies have shown that the corn and wheat endophyte, Sarocladium zeae, produce pyrrocidines that suppress production of fumonisin, a mycotoxin produced by F. verticillioides. In this study, we discovered that S. zeae also suppressed production of 15-acetylDON (15-ADON) in a trichothecene induction medium when co-cultured with F. graminearum. The suppression of 15-ADON production was not due to growth inhibition of F. graminearum or degradation of 15-ADON by S. zeae. Additionally, the suppression was neither caused by pyrrocidines, nor correlated with presence of pyrrocidine synthesis genes in S. zeae. This suggests a novel mechanism of suppression of trichothecene production. Therefore, we used transcriptomic and metabolomic approaches to investigate the mechanism by which S. zeae suppresses 15-ADON production. Our preliminary analyses showed that the expression of trichothecene biosynthetic genes was down regulated in F. graminearum and S. zeae co-cultures compared to F. graminearum mono-cultures. Furthermore, we tested over 30 S. zeae strains and found that 20 of them inhibited 15-ADON production in co-cultures. Interestingly, we found different secondary metabolite profiles in strains that suppressed toxin production compared to those that did not suppress toxin production in cocultures of S. zeae and F. graminearum. This study will improve our understanding of how S. zeae interacts with F. graminearum to inhibit toxin production and could lead to a novel strategy to control FHB and mycotoxin contamination.