Crohn’s disease is a relapsing and remitting inflammatory disorder with a variable clinical course. Although most patients present with an inflammatory phenotype (B1), approximately 20% of patients rapidly progresses to complicated disease, which includes stricturing (B2) within 5 years. We analyzed DNA methylation patterns in blood samples of pediatric patients with Crohn’s disease at diagnosis and later time points to identify changes that associate with and might contribute to disease development and progression.