Background: Prevalence of inflammatory bowel disease (IBD) is increasing in Egypt. Multiple lines of biological treatment have been but still there is failure of treatment to these medications and because of high cost it is of great importance to personalize treatment options. Aim of the study: This study aimed to assess the factors that can predict the response to biological treatment. Subjects and methods: This study included 133 patients with IBD who were indicated to biological treatment (AntiTNF), and followed up for 2 years. All demographic, clinical laboratory data and disease activity were recorded at 1st presentation. Patient were classified into 2 groups one group who showed nonresponse to treatment and the other one who responded well to treatment. All factors were analyzed as predictors of nonresponse using univariate and multiple regression. Results: Out of 133 patients of IBD, 77 patient showed non-response. Younger age, family history of IBD, long duration of disease, previous surgical resection and presence of extraintestinal manifestation could be predictors of non-response. Increased levels of inflammatory markers of ESR, CRP and fecal calprotectin were associated with poor response to therapy (p value < 0.001, < 0.001 and 0.001 respectively). Moreover, increased activity and colonic extent in UC associated with nonresponse also marked activity and behavior of CD patients could be predictive factors of relapse. In multivariable analysis the factors independently associated with non-response were younger age, long duration of disease, presence of extraintestinal manifestations, elevated ESR and fecal calprotectin. Conclusions: Multiple disease related factors can be associated and could predict the response to anti-TNF treatment. Keywords: Inflammatory bowel disease, biological treatment, Anti-TNF, non-response to treatment.